gastrins and Obesity

This review describes the premises for accurate measurement of the gut hormone and satiety factor cholecystokinin (CCK) in circulation. Such a description is useful for nutrition and obesity research in which CCK in its satiety role has evoked considerable interest during the last decades. The background for the review is two sorts of considerations or concerns. First, CCK is a complex peptide system that in several ways challenges plasma measurements because the concentrations in plasma are very low (in the femtomolar to low picomolar range), and the bioactive CCK circulates in different molecular forms (CCK-58, -33, -22, and -8). Furthermore, there are major specificity problems because the structurally similar gastrin hormone circulates in 10- to 20-fold higher concentrations, and in addition, plasma proteins may, due to their high concentration, interfere in an unspecific way with immunoassay measurements. The second concern is that several obesity studies in recent decades have been based on commercial CCK kits with often inadequate documentation of the reliability in plasma measurement. Consequently, many plasma CCK results in today's obesity studies are difficult to compare. Moreover, the use of even fairly reliable commercial CCK kits has recently suffered from sudden discontinuation of the kit production, which has endangered several projects in nutrition and obesity research.

Topics: Animals; Appetite Regulation; Bias; Biomedical Research; Blood Chemical Analysis; Blood Proteins; Cholecystokinin; Gastrins; Humans; Nutritional Sciences; Nutritional Status; Obesity; Peptide Fragments; Plasma; Satiety Response

Obesity and its comorbidities, such as type 2 diabetes mellitus and cardiovascular disease, constitute growing challenges for public health and economies globally. The available treatment options for these metabolic disorders cannot reverse the disease in most individuals and have not substantially reduced disease prevalence, which underscores the unmet need for more efficacious interventions. Neurobiological resilience to energy homeostatic perturbations, combined with the heterogeneous pathophysiology of human metabolic disorders, has limited the sustainability and efficacy of current pharmacological options. Emerging insights into the molecular origins of eating behaviour, energy expenditure, dyslipidaemia and insulin resistance suggest that coordinated targeting of multiple signalling pathways is probably necessary for sizeable improvements to reverse the progression of these diseases. Accordingly, a broad set of combinatorial approaches targeting feeding circuits, energy expenditure and glucose metabolism in concert are currently being explored and developed. Notably, several classes of peptide-based multi-agonists and peptide-small molecule conjugates with superior preclinical efficacy have emerged and are currently undergoing clinical evaluation. Here, we summarize advances over the past decade in combination pharmacotherapy for the management of obesity and type 2 diabetes mellitus, exclusively focusing on large-molecule formats (notably enteroendocrine peptides and proteins) and discuss the associated therapeutic opportunities and challenges.

Topics: Animals; Body Mass Index; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Male; Metabolic Diseases; Metformin; Mice; Molecular Targeted Therapy; Obesity; Prognosis; Risk Assessment; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome

Topics: Animals; Blood Glucose; Bone and Bones; Energy Metabolism; Gastrins; Gastrointestinal Hormones; Gastrointestinal Microbiome; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Mice; Obesity; Sensitivity and Specificity

Topics: Amino Acids; Animals; Blood Glucose; Digestion; Eating; Endorphins; Fatty Acids; Gastrins; Gastrointestinal Hormones; Histamine; Humans; Intestinal Absorption; Obesity; Prostaglandins; Somatostatin; Vagus Nerve

Topics: Cholecystokinin; Diabetes Mellitus, Type 2; Digestive System Physiological Phenomena; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Insulin; Motilin; Neurotensin; Obesity; Pancreatic Polypeptide; Pentagastrin; Secretin; Somatostatin; Vasoactive Intestinal Peptide

The lining of the intestinal tract is constantly renewed in a brisk but orderly fashion. Further acceleration of cell renewal is elicited by various stimuli, notably surgical shortening of the intestine and hyperphagia, which lead to prompt but persistent increases in mucosal mass. Progressive hypoplasia ensues when the small and large bowel are deprived of their normal contents, either by fasting (with or without parenteral nutrition) or by exclusion from intestinal continuity. All atrophic changes are reversed by refeeding or restoration of the normal anatomical disposition. Intestine responds to mucosal damage by regeneration from the crypts. Pancreatobiliary secretions mediate some of the tropic effects of chyme; systemic influences, both neurovascular and humoral, also play a part in the adaptive response of the gut.

Topics: Adaptation, Physiological; Adult; Animals; Cell Division; Colectomy; Colostomy; Female; Gastrins; Glucagon-Like Peptides; Humans; Hyperphagia; Hyperplasia; Hypertrophy; Ileum; Intestinal Diseases; Intestinal Mucosa; Intestines; Jejunum; Obesity; Parenteral Nutrition; Rats; Starvation

1. The insulinogenic factor of the gastrointestinal mucosa named "incretin" is only one part of the complex enteroinsular axis. --2. Of the chemically defined gastrointestinal hormones GIP is the strongest incretin candidate. --3. Because of the dual function of GIP as gastrone and insulinotropic substance several safeguards against GIP-mediated insulin hypoglycaemia exist. --4. No pathological condition has yet been found which is causally related to hyper- or hyposecretion of GIP. However, an exaggerated GIP response (usually secondary to the disease) may participate in the pathogenesis of hyperinsulinaemia of patients with obesity and duodenal ulcer. --5. The injection of GIP antibodies only partially abolishes the incretin effect. Therefore, GIP, although important, is not the only incretin.

Topics: Absorption; Diabetes Mellitus; Feedback; Gastrins; Gastrointestinal Hormones; Humans; Insulin; Insulin Secretion; Neurotransmitter Agents; Obesity; Peptides; Vagus Nerve

Topics: Adult; Age Factors; Aged; Animals; Body Constitution; Body Weight; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Energy Metabolism; Fasting; Female; Gastrins; Humans; Male; Middle Aged; Nutrition Disorders; Obesity; Protein Deficiency; Somatotypes

A group of 13 consecutive regularly menstruating women who gained at least 5 kg the previous year (Group I) was compared to a control group of similar age, parity, and social class (Group II). The two groups were similar in estimated and observed food intakes; pre- and postprandial gastrin levels; hourly 24-h profiles of cortisol and insulin; urinary cortisol and 17-hydroxycorticosteroids. Group I had higher serum prolactin concentrations at all times than Group II (mean values 14.60 micrograms/l vs. 8.84 micrograms/l; p = .0121). Galactorrhea was observed in 5 women from Group I and in none of the women from Group II (p < .05). Group I also differed from Group II in a higher incidence of meaningful life-events the year preceding the study, higher prevalence of sexual dysfunction (9/13 vs. 4/13; p < .01) and higher indexes (p < .05) of several parameters in the MMPI and SCL 90. Median serum cortisol and prolactin concentrations were negatively correlated, both in Group I (R = -.669; p = .012) and in the whole sample (R = -.453; p = .0298). It is suggested that the rapid weight gain is part of a neuroendocrine response to environmental stimuli also characterized by hyperprolactinemia. The significant negative correlation between serum prolactin and cortisol indicates that this response differs from, and is possibly an alternative to, the sympathoadrenal "stress" response.

Topics: Adult; Energy Intake; Feeding Behavior; Female; Gastrins; Hormones; Humans; Hydrocortisone; Insulin; Life Change Events; Obesity; Personality Assessment; Pituitary Neoplasms; Prolactin; Prolactinoma; Pseudopregnancy; Psychophysiologic Disorders; Reference Values; Stress, Psychological; Weight Gain

A study was conducted to test the efficacy and safety of a 300 ml silicone-rubber gastric balloon for weight reduction. Eighty-six obese subjects were distributed into four groups: (1) gastric balloon only, (2) gastric balloon and prescribed 1000 kcal/day (239 kJ) diet, (3) 1000 kcal/day diet only, and (4) no treatment. The intervention period was 3 months. The balloon only group lost 3.2 kg +/- 0.9 (s.e.), the balloon and diet group lost 5.1 +/- 1.0 kg, the diet group lost 6.9 +/- 1.4 kg and the control group gained 0.6 +/- 0.5 kg. The three intervention groups each lost significantly more weight than the control group. The diet only group lost significantly more weight than the balloon only group. Body densitometry showed that the treatment groups lost a significant amount of body fat. Gastroscopy revealed three ulcers and two superficial erosions at balloon removal. The gastric balloons were well tolerated despite gastric spasms and nausea which abated after the initial 24-48 hours. Gastric capacity was determined in a subset of 19 subjects from the two balloon groups before the intervention by distending the stomach with a balloon and calculating the volume required to produce an increase in intragastric pressure of 5 cm H2O. Subjects with a smaller gastric capacity lost more weight with the balloon than subjects with a large capacity (r = 0.45, P less than 0.05). These results suggest that for improved efficacy, balloon volume may need to be larger than 300 ml or adjusted to the individual's gastric capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Body Composition; Diet, Reducing; Energy Intake; Female; Follow-Up Studies; Gastric Balloon; Gastrins; Humans; Male; Obesity; Stomach; Stomach Ulcer; Weight Loss

The aim of the study was to elucidate the differential role of the jejunum and ileum in the regulation of secretion of the gut hormones, gastrin, gastric inhibitory polypeptide, and enteroglucagon, and the pancreatic hormones, insulin, glucagon, and pancreatic polypeptide, in man. We measured the plasma levels of the hormones (and glucose) during fasting and after a test meal in 34 obese patients, of whom 5 were waiting for bypass surgery and 29 had had a jejunoileal bypass with a 3:1 or 1:3 jejunoileal ratio between the functioning segments 3, 9, or 15 months earlier. The major findings were that surgery bypass (1) has no important influence on the levels of gastrin and pancreatic polypeptide, (2) reduces the level of gastric inhibitory polypeptide, insulin (and glucose), and enhances the pancreatic glucagon level, independently of the jejunoileal ratio, and (3) increases enteroglucagon secretion, most effectively so with a short jejunal and long ileal segment left in continuity. These findings suggest that the upper jejunum and terminal ileum has no important role in regulation of secretion of these hormones apart from that in secretion in enteroglucagon which is related to the length of functioning ileum.

Topics: Adult; Female; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Ileum; Insulin; Jejunum; Male; Middle Aged; Obesity; Pancreatic Hormones; Pancreatic Polypeptide

Meal-stimulated gastric acid secretion was measured by intragastric titration before and after jejuno-ileal bypass operation in five obese patients. Acid secretion was significantly reduced after the operation, particulary during the late phase of the acid response, suggesting that stimulation of acid secretion may be elicited from the upper small intestine by a composite meal. Serum gastrin concentrations remained unchanged after the operation.

Topics: Adult; Female; Food; Gastric Juice; Gastrins; Humans; Intestine, Small; Middle Aged; Obesity; Secretory Rate

Fundectomy, shown as an alternative to restrictive techniques, causes absorption restriction and metabolic changes. This study aimed to examine the histopathological changes caused by the fundectomy as a technique applied to rats by hormones that affect stomach and obesity metabolism and its effect on weight loss.. 2randomly selected Winstar-Hannover rat groups were evaluated by measuring their pre-and postoperative weights and biochemically measuring Gastrin, Ghrelin, and Leptin levels on day 30. After sacrification, the stomachs were taken for histopathological examination.. Significant weight loss was observed in the fundectomy group in the 1stmonth postoperatively. Biochemically, Gastrin means in the fundectomy group were statistically significantly higher than in the control group. The mean Ghrelin and Leptin levels of the Fundectomy Group were statistically significantly lower (p=0.005). Immunohistochemically, Gastrin means ™at the antrum and proximal stomach parts of the Fundectomy Group were significantly higher than in the control group. As Ghrelin, a significant decrease was observed in all 3regions of the Fundectomy Group compared to the control group. Leptin results were significantly lower at the antrum and proximal stomach parts of the Fundectomy Group. Histopathologically, in the Fundectomy Group, cystic glandular hyperplasia was moderate at the proximal stomach, foveolar hyperplasia was mild at the antrum, fibrosis was moderate at the antrum and corpus, and high at the proximal stomach.. Fundectomy is an effective method in terms of weight loss. This animal experiment, conducted as a pilot study, will be an essential step in elucidating metabolic and histopathological changes.. Bariatric surgery, Fundectomy, Obesity.. La resezione del fondo gastrico, indicata come alternativa alle tecniche restrittive, provoca restrizione dell’assorbimento e alterazioni metaboliche. Questo studio mirava a esaminare i cambiamenti istopatologici causati da questo intervento eseguito su ratti ad opera di ormoni che influenzano il metabolismo dello stomaco e dell’obesità e il suo effetto sulla perdita di peso. Sono stati utilizzati 2 Gruppi di ratti Winstar-Hannover, selezionati casualmente, valutando il loro peso pre e postoperatorio e misurando biochimicamente i livelli di gastrina, grelina e leptina al giorno 30. Dopo il sacrificio, gli stomaci sono stati sottoposti ad esame istopatologico. RISULTATI: È stata osservata nel 1° mese dopo l’intervento una significativa perdita di peso nel gruppo dei resecati del fondo gastrico. Dal punto di vista biochimico, i livelli medi della Gastrina è risultato statisticamente e significativamente più elevato nel gruppo dei gastroresecati rispetto al gruppo di controllo. I livelli medi di grelina e leptina sono risultati statisticamente e significativamente più bassi (p=0,005) nel gruppo dei gastroresecati. Dal punto di vista immuno-istochimico i livelli medi della Gastrina sono risultati significativamente più elevati nelle parti dell’antro e dello stomaco prossimale nel gruppo dei gastro-resecati rispetto al gruppo di controllo. Per quanto riguarda la Grelina, è stata osservata una diminuzione significativa in tutte e 3 le regioni del gruppo della fundectomia rispetto al gruppo di controllo. I risultati della leptina sono risultati significativamente più bassi nelle parti dell’antro e dello stomaco prossimale del gruppo dei fundectomizzati. Dal punto di vista istologico nel gruppo della fundectomia, l’iperplasia ghiandolare cistica era moderata nello stomaco prossimale, l’iperplasia foveolare era lieve all’antro, la fibrosi era moderata all’antro e al corpo ed elevata nello stomaco prossimale. CONCLUSIONE: la fundectomia si è dimostrata un metodo efficace ai fini della riduzione del peso. Questo studio sperimentale sugli animali, condotto come studio pilota, potrà rappresentare un passaggio essenziale per chiarire i cambiamenti metabolici e istopatologici della resezione del fondo gastrico.

Topics: Animals; Gastrins; Ghrelin; Hyperplasia; Leptin; Obesity; Pilot Projects; Rats; Weight Loss

The duodenal-jejunal bypass sleeve ((DJBS) or EndoBarrier Gastrointestinal Liner) induces weight loss in obese subjects and may improve glucose homeostasis in patients with type 2 diabetes (T2D). To explore the underlying mechanisms, we evaluated postprandial physiology including glucose metabolism, gut hormone secretion, gallbladder emptying, appetite and food intake in patients undergoing DJBS treatment.. A total of 10 normal glucose-tolerant (NGT) obese subjects and 9 age-, body weight- and body mass index-matched metformin-treated T2D patients underwent a liquid mixed meal test and a subsequent ad libitum meal test before implantation with DJBS and 1 week (1w) and 26 weeks (26w) after implantation.. At 26w, both groups had achieved a weight loss of 6 to 7 kg. Postprandial glucagon-like peptide-1 (GLP-1) and peptide YY responses increased at 1w and 26w, but only in T2D subjects. In contrast, glucose-dependent insulinotropic polypeptide responses were reduced only by DJBS in the NGT group. Postprandial glucose, insulin, C-peptide, glucagon, cholecystokinin and gastrin responses were unaffected by DJBS in both groups. Satiety and fullness sensations were stronger and food intake was reduced at 1w in NGT subjects; no changes in appetite measures or food intake were observed in the T2D group. No effect of DJBS on postprandial gallbladder emptying was observed, and gastric emptying was not delayed.. DJBS-induced weight loss was associated with only marginal changes in postprandial physiology, which may explain the absence of effect on postprandial glucose metabolism.

Topics: Adult; Appetite; Bariatric Surgery; Blood Glucose; Body Composition; C-Peptide; Case-Control Studies; Cholecystokinin; Comorbidity; Diabetes Mellitus, Type 2; Eating; Female; Gallbladder Emptying; Gastric Emptying; Gastric Inhibitory Polypeptide; Gastrins; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Insulin; Male; Middle Aged; Obesity; Peptide YY; Postprandial Period; Prospective Studies; Satiety Response; Treatment Outcome

Recent investigations have linked elevated gastrin levels to the improvement of type 2 diabetes mellitus (T2DM). Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are effective treatments for T2DM, but it is not known if this is related to postoperative alterations of gastrin secretion.. Twenty women previously operated with RYGB or SG and 13 female controls were enrolled and evaluated for body mass index, lipids, C-peptide, HbA1c, and anti-H. pylori IgG. Glucose, gastrin, insulin, and glucagon-like peptide 1 (GLP-1) concentrations were measured before and 30, 60, 90, and 120 min after ingestion of a protein-rich mixed meal.. Six participants primarily selected were excluded due to usage of proton pump inhibitors, positive H.pylori IgG, or history of T2DM, yielding the following groups: RYGB (n = 9), SG (n = 8), and controls (n = 10). There were no differences in age, body mass index, HbA1c, or C-peptide levels between groups. RYGB had significantly lower area under the curve (AUC) for glucose during the test compared to controls (p = 0.013). RYGB showed lower serum gastrin levels compared to SG and controls (p < 0.05 for all). There was a non-significant increased gastrin release in SG compared to controls (p = 0.091). For SG and controls, there was a negative correlation between glucose and gastrin response (p = 0.0043).. Gastrin secretion is diminished after RYGB. Hypergastrinemia was not present after SG, but a tendency of enhanced gastrin secretion was observed. These findings require further investigation in prospective studies.

Topics: Adult; Aged; Blood Glucose; Dietary Proteins; Female; Gastrectomy; Gastric Bypass; Gastrins; Glucagon-Like Peptide 1; Humans; Insulin; Middle Aged; Obesity; Pilot Projects; Prospective Studies

In addition to its glucoregulatory actions, exendin-4, a stable glucagon-like peptide-1 receptor agonist, exhibits protective effects in the pancreas and anti-obesity effects. Suitable combination treatment with other anti-obesity or pancreas protective agents would be an effective approach to optimize these additional effects. In the present study, we investigated the effects of the addition of omeprazole, a proton pump inhibitor, to exendin-4 in db/db mice, an experimental model of obesity and type 2 diabetes.. The effects repeated dose treatment for 14 days with exendin-4 (8 μg/kg, s.c.) and omeprazole (30 mg/kg, s.c.) on glycemic control, food intake, and body weight were determined in obese and hyperglycemic db/db mice. The effects of these treatments on plasma gastrin, ghrelin, and leptin levels were determined, along with effects on nausea-like symptoms. The pancreatic effects of the repeated dose treatment were assessed by measuring %HbA1c in the circulation as well as pancreatic insulin and glucagon content and glucokinase activity.. Combination treatment resulted in significant decreases in plasma leptin and ghrelin levels after repeated dosing. Omeprazole improved the anorectic and body weight-lowering effects and reversed the inhibitory effect of exendin-4 on gastrin levels after repeated dose treatment. The 14-day combination treatment significantly reduced glucose excursion and improved insulin levels, with a concomitant decrease in %HbA1c levels. It also improved glucokinase activity and pancreatic insulin content, with a significant decrease in glucagon content.. Combined treatment with omeprazole with exendin-4 reduces food intake and body weight gain, most likely through changes in plasma ghrelin and leptin levels, and improves pancreatic insulin and glucagon content by improving glucokinase activity.

Topics: Animals; Anti-Obesity Agents; Body Weight; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Gastrins; Glucagon; Hypoglycemic Agents; Insulin Resistance; Leptin; Male; Mice; Mice, Inbred Strains; Mice, Obese; Obesity; Omeprazole; Peptides; Venoms

Metabolic syndrome (MS), defined as central obesity, hyperinsulinemia, insulin resistance, hypertension, dyslipidemia and glucose intolerance, has been associated with inflammatory biomarkers and cardiovascular diseases. This study was carried out on three groups of women; lean controls, moderately obese with MS (OB-MS) and morbidly obese with MS (MOB-MS). The main objectives were: 1. to analyze the plasma levels of total and acylated ghrelin, peptide YY(3-36) (PYY(3-36)), cholecystokinin (CCK), gastrin and insulin levels under basal conditions and in response to a standard mixed meal, and 2. to elucidate the relationship between the plasma levels of these gut peptides and metabolic syndrome parameters. Plasma levels of the gut hormones were measured by radioimmunoassays at time 0 just before the meal and at 30, 60 and 120 min after a meal ingestion. Traditional lipid profile and high-sensitivity C reactive protein (hs-CRP), the strongest biomarker of inflammation were also determined in OB-MS and MOB-MS. When compared to OB-MS, MOB-MS exhibited much higher anthropometric parameters such as waist circumference, higher fat mass and higher plasma levels of low density lipoprotein-cholesterol (LDL-C) and hs-CRP. Both these obese groups revealed significantly higher values of body mass index (BMI), fat mass, total cholesterol (TC), LDL-C, fasting glucose, fasting insulin, insulin resistance (IR) calculated from homeostatic model assessment (HOMA) and hs-CRP compared to the values recorded in lean subjects. Fasting PYY(3-36) level was lower, while fasting acylated ghrelin was higher in MOB-MS than in OB-MS. Plasma total and acylated ghrelin levels were significantly lower in OB-MS compared to lean women. In MOB-MS women the fasting PYY(3-36) levels were lower compared to lean controls and OB-MS, whilst postprandially in both OB-MS and MOB-MS, it was much lower than in lean women. The fasting plasma levels of total and acylated ghrelin and their postprandial decrease were significantly smaller in both obese groups compared to lean subjects. Plasma hs-CRP levels correlated positively with BMI, waist circumference, fat mass, fasting glucose, HOMA IR and fasting active ghrelin, whilst it negatively correlated with plasma fasting and total ghrelin. Moreover, plasma fasting acylated ghrelin correlated positively with fat mass. Fasting total ghrelin correlated positively with BMI, HDL-C and negatively with HOMA IR. We conclude that MS features of obesity are closely

Topics: Acylation; Adult; Blood Glucose; Body Mass Index; C-Reactive Protein; Cholecystokinin; Cholesterol, LDL; Fasting; Female; Gastrins; Gastrointestinal Hormones; Ghrelin; Humans; Insulin; Insulin Resistance; Metabolic Syndrome; Obesity; Obesity, Morbid; Peptide Hormones; Peptide YY; Poland; Postprandial Period

Maternal obesity has been reported as a risk factor for various maternal and fetal complications. The aim of the present study was to examine the patterns of basal and postprandial plasma concentrations of certain gut hormones affecting food intake such as acylated ghrelin, peptide YY(3-36) (PYY(3-36)), cholecystokinin (CCK), insulin and glucose in pregnant women with varying body mass gain during physiological pregnancy. The study included 34 women with singleton pregnancies in the 2(nd) trimester of gestation. The examined pregnant women were divided into 4 groups; I. control pregnancy (CP) with weight gain below 0.5 kg/week; II. overweight low weight gain <1 kg/week (OLWG), III. overweight high weight gain >1 kg/week (OHWG); morbidly obese pregnant with weight gain >1.5 kg/week (MOP). The basal acylated-ghrelin levels in MOP subjects were significantly higher than those in CP and no usual suppression of acylated ghrelin after the meal observed in CP as well as in OLWG and OHWG was found in MOP women. Basal PYY(3-36) plasma levels were similar in CP, OLWG and OHWG but in MOP was significantly reduced and no significant increase in hormone level, typically observed in CP, was detected after a meal in overweight or obese women studied. The fasting CCK and C-reactive protein (CRP) levels in MOP subjects were significantly higher than those in CP and other overweight women. In conclusion, we found that pregnant women with overweight and obesity exhibit significant changes in fasting and postprandial gut hormones affecting food intake such as acylated ghrelin, PYY(3-36) and CCK as well as in CRP and these changes might contribute, at least in part, the development of obesity in pregnancy.

Topics: Acylation; Adult; Appetite; Blood Glucose; Body Mass Index; C-Reactive Protein; Cholecystokinin; Fasting; Female; Gastrins; Gastrointestinal Hormones; Ghrelin; Homeostasis; Humans; Insulin; Obesity; Obesity, Morbid; Peptide Hormones; Peptide YY; Poland; Postprandial Period; Pregnancy; Pregnancy Complications; Weight Gain

The authors recently reported that gastrin gene knockout (GAS-KO) mice had an increased risk for colon carcinogenesis in response to azoxymethane (AOM) compared with their wild type (WT) littermates. In the current report, the authors discuss the predisposition of GAS-KO mice to develop obesity and metabolic hormonal changes that may contribute to their increased risk of colon carcinogenesis.. The weight and deposition of fat was monitored in the mice over a 14 month period, using magnetic resonance imaging and nuclear magnetic resonance techniques. Changes in plasma concentrations of ghrelin, leptin, insulin, and glucose were assessed using radioimmunoassay analysis and enzyme-linked immunosorbent assays. Preneoplastic markers of colon carcinogenesis (aberrant crypt foci [ACFs]), in response to AOM, were measured in a subset of obese versus lean GAS-KO mice and were compared with the markers in WT mice.. Increases in visceral adiposity were evident by age 2 months in GAS-KO mice, resulting in macroscopic obesity by age 7 months. Hyperinsulinemia and insulin:glucose ratios were increased significantly in GAS-KO mice as young as 1 month and preceded alterations in nonfasting leptin and ghrelin levels. The number of ACFs per mouse colon were increased significantly in the following order: obese GAS-KO mice > lean GAS-KO mice > WT mice. Fasting plasma insulin levels were 0.88 +/- 0.1 ng/mL, 1.45 +/- 0.3, and 2.76 +/- 0.9 ng/mL in the WT, GAS-KO lean, and GAS-KO obese mice, respectively.. The current results suggest the novel possibility that loss of amidated gastrins may increase adipogenesis, hyperinsulinemia, and colon carcinogenesis in GAS-KO mice. The increase in colon carcinogenesis may be due in part to hyperinsulinemia, increased obesity, and other associated hormone changes that were measured in GAS-KO mice.

Topics: Animals; Azoxymethane; Body Weight; Carcinogens; Colonic Neoplasms; Gastrins; Gene Expression; Ghrelin; Glucose; Hyperinsulinism; Insulin; Insulin Resistance; Leptin; Magnetic Resonance Imaging; Male; Mice; Mice, Knockout; Obesity; Peptide Hormones; Precancerous Conditions; Radioimmunoassay; Thinness

The current studies were initiated to investigate the role of brain-gut peptide, gastrin, on locomotor activity and anxiety-like behavior. Young, male mutant mice, lacking gastrin gene expression (GAS-KO mice), were used in the experiments. The locomotor activity of GAS-KO vs wild type (WT) mice was compared by open field test. The anxiety-like behavior was examined using elevated plus maze. The time and entries to the open arms of the elevated plus maze were used as an indicator for the anxiety-like behavior and the data were analyzed using Hindsight program. On the open field test, locomotor activity of GAS-KO mice was similar to that of the WT mice for the first 10 min of the test, but decreased significantly after that. Anxiety-like behavior was more evident in the GAS-KO vs WT mice in the elevated plus maze experiments. The number of entries to and time spent on the open arms of plus-maze were significantly reduced for the GAS-KO vs WT mice suggesting an increased anxiety-like behavior of GAS-KO mice. Our studies suggest that normal circulating levels of gastrins may play a direct or indirect role in the regulation of locomotor activity and anxiety-like behavior.

Topics: Animals; Anxiety; Avoidance Learning; Behavior, Animal; Dietary Carbohydrates; Dietary Fats; Exploratory Behavior; Gastrins; Gene Expression; Male; Maze Learning; Mice; Mice, Inbred ICR; Mice, Knockout; Motor Activity; Obesity

In obese patients, jejunoileal bypass (JIB) has been used to induce weight reduction. Changes in the neuroendocrine system may be affected by the JIB-operation, because the proximal small intestinal mucosa has a rich supply of endocrine cells and peptidergic nerves.. In 37 obese patients operated with JIB 1-30 years ago, small intestinal biopsies were taken at the duodeno-jejunal flexure, proximal to the anastomosis and from 5 unoperated obese persons and 20 normal weight patients. The tissue specimens were processed for immunocytochemical demonstration of cells/nerves containing: gastrin, cholecystokinin (CCK), secretin, gastric inhibitory peptide (GIP), motilin, somatostatin, serotonin, glicentine, peptide YY (PYY), neurotensin, vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY) and galanin. The number of different endocrine cell-types were counted per unit length of mucosa, and the density of the peptidergic nerves was assessed semiquantitatively according to a schematic scale.. JIB-patients had an increased density of CCK and somatostatin cells in the duodenal mucosa. The CCK cells displayed a changed reaction pattern, with a greater cell number reacting with an antiserum directed towards a non-amidated mid-sequence of procholecystokinin compared with the other groups. In obese unoperated patients, the density of PYY and secretin cells was decreased compared with the JIB-patients and the density of the GIP cells compared with both other groups.. JIB induces an up-regulation of somatostatin and CCK precursor-containing cells in the duodenal mucosa. The time duration after the JIB did not seem to influence the results.

Topics: Adolescent; Adult; Aged; Cell Count; Cholecystokinin; Duodenum; Enteroendocrine Cells; Female; Follow-Up Studies; Gastrins; Hormones; Humans; Jejunoileal Bypass; Male; Middle Aged; Obesity; Somatostatin; Somatostatin-Secreting Cells; Time Factors

Cholecystokinin (CCK) and gastrin (G) and their receptors (CCK1 and CCK2) are involved in multiple physiological functions. Notably, CCK1R plays a role in the regulation of food intake whereas both CCK1R and CCK2R play a role in the regulation of pancreatic endocrine function. CCK1R and CCK2R may therefore serve as pharmacological targets in diabetes and obesity and genes encoding these receptors may be candidate genes in the pathogenesis of the diseases. In this study, we used single nucleotide polymorphism analysis and allele specific amplification for mutation screening of the CCK2 receptor gene and family linkage study. Mutated receptors were constructed, expressed in COS-7 cells for analysis of their binding and functional properties. V125I-CCK2 receptor variant was found in 2 out of 18 type 2 diabetes mellitus families tested. V125I mutation co-segregated in those 2 initial families, but further association studies showed that this mutation was not associated with diabetes or early age at diagnosis of the disease. V125I-CCK2 receptor high affinity sites exhibited a 2-fold enhanced binding affinity for CCK which was correlated to a slightly increased potency in coupling to inositol phosphate production. Since CCK2 receptor is expressed in pancreatic glucagon-producing cells in humans and is involved in secretion of glucagon, an increase of binding affinity of the mutated CCK2 receptor could enhance glucagon secretion in patients bearing V125I mutation. We also characterized a mutant of the CCK1 receptor which was previously identified in an obese patient. This mutant, V365I-CCK1, demonstrated a decreased level of expression (26%) and efficacy (25%) to stimulate inositol phosphates. It can therefore be expected that in humans bearing V365I mutation, decreases in CCK1 receptor expression and coupling efficiency may affect CCK-induced regulation of satiety. Polymorphism or mutations in the CCK receptors may be involved in type 2 diabetes mellitus and obesity. However, further studies are necessary to precisely evaluate this role in humans.

Topics: Amino Acid Sequence; Binding Sites; Diabetes Mellitus; Diabetes Mellitus, Type 2; DNA Primers; Gastrins; Gene Frequency; Genetic Linkage; Genotype; Humans; Inositol Phosphates; Middle Aged; Molecular Sequence Data; Mutagenesis, Site-Directed; Obesity; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Receptor, Cholecystokinin A; Receptor, Cholecystokinin B; Receptors, Cholecystokinin

An obese mouse model (Cpefat/Cpefat) that has hyperproinsulinemia and late onset obesity has been described. Cpefat/Cpefat mice have a missense mutation in carboxypeptidase E (CPE), a processing enzyme essential for production of biologically active endocrine and neuroendocrine peptides. We have reported previously that CPE activity was absent in the antrum of the stomach and that processing of progastrin to the amidated biologically active form of gastrin is reduced. Since gastrin is a major secretagogue for gastric acid secretion, the purpose of the present experiments was to examine gastric acid secretion in Cpefat/Cpefat mice. In addition, secretion of amidated gastrin in response to inhibition of acid secretion was tested in Cpefat/Cpefat. Both gastric acid and challenged gastrin secretion are reduced in Cpefat/Cpefat mice. We conclude that stomach CPE activity is essential for gastric secretory activity and for challenged gastrin release.

Topics: Animals; Carboxypeptidase H; Carboxypeptidases; Famotidine; Gastric Acid; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Mice; Mice, Obese; Mutation, Missense; Obesity; Proinsulin

Plasma concentrations of regulatory peptides were monitored in groups of obese and normal-weight subjects following modified sham feeding and a liquid fatty meal. Following modified sham feeding a significant increase in immunoreactive cholecystokinin (CCK) in plasma was recorded in both groups. In the obese subjects, however, the concentrations following sham feeding were significantly lower than in normal-weight subjects, and the initial part of the response was negative. Basal and modified sham feeding stimulated immunoreactive pancreatic polypeptide (PP) concentrations in plasma did not differ between the groups. After the liquid fatty meal plasma CCK concentrations increased similarly in both groups. In contrast immunoreactive neurotensin and somatostatin concentrations following the meal were lower in the obese group, and a changed concentration-time pattern for somatostatin was observed in the obese group. Postprandial concentrations of PP and immunoreactive gastrin were not different in the groups. The results indicate that the plasma concentration patterns of CCK, somatostatin and NT are disarranged in obesity. The changes may promote rapid propulsion and absorption of ingested food, and facilitate deposition of fat in adipose tissue in obesity and thus may be of pathophysiological importance.

Topics: Adult; Blood Glucose; Cholecystokinin; Female; Food; Gastrins; Humans; Middle Aged; Neurotensin; Obesity; Pancreatic Polypeptide; Radioimmunoassay; Somatostatin

It has been hypothesized that G-cell hyperplasia secondary to increased food consumption in the obese Zucker rat was responsible for the hypergastrinemia observed in vivo and from the isolated perfused stomach preparation. This possibility was investigated in pair-feeding experiments wherein the food intake of obese animals was restricted to match that of lean littermates from 5 to 8 weeks of age. Dietary restriction reduced the antral G-cell population of the obese rat to a similar level as that seen in lean animals, supporting the view that hyperphagia is the trigger for G-cell hyperplasia. However, basal gastrin levels measured in vivo and in vitro from the stomach preparation of the pair-fed obese animals were not significantly lower than those of obese animals fed ad libitum. Thus, abnormal feeding behavior in the obese phenotype cannot be directly related to gastrin hypersecretion and G-cell hyperplasia is not the primary cause of hypergastrinemia.

Topics: Animals; Body Weight; Diet; Eating; Gastrins; Models, Biological; Obesity; Pyloric Antrum; Rats; Rats, Zucker

In this study, gastrin release in the obese Zucker rat was investigated by in vivo and in vitro experiments. Obese rats exhibited normal plasma gastrin levels at 3 weeks (preobese), were moderately hypergastrinemic at 3 months and severely hypergastrinemic at 5 months, compared to lean littermates. Following oral peptone, plasma gastrin levels doubled in both lean and obese rats. Basal and vagally stimulated gastrin release from perfused stomachs was greater in obese compared to lean rats and atropine had no effect on basal gastrin release in either group. Basal somatostatin release from the perfused stomach was found not to differ in both groups of animals. Morphological studies revealed an increase in the number of gastrin-containing G-cells in adult obese rats compared to lean littermates, but not in 3-week-old pups compared to lean littermates, indicating a strong correlation between cell number and plasma gastrin levels. These data indicate that the obese Zucker rat exhibits fasting hypergastrinemia in vivo, a condition which appears after weaning and increases in severity with age. Gastrin hypersecretion persists from the vascularly perfused stomach preparation. The basal hypergastrinemia of the obese Zucker rat is independent of a hyperactive postganglionic cholinergic drive but is associated with and probably causally related to an increase in antral G-cell numbers.

Topics: Animals; Atropine; Gastric Mucosa; Gastrins; Immunohistochemistry; Obesity; Radioimmunoassay; Rats; Rats, Zucker; Somatostatin; Vagus Nerve

In order to evaluate the effectiveness of a gastric implant in an animal model of dietary obesity, silicone implants (2.5 ml) were inserted into the stomachs of male rats maintained on a chow or "cafeteria" diet. At the time of implantation, the cafeteria fed rats weighed 14% more than chow fed controls. Overweight cafeteria fed animals lost weight in response to the gastric implant, whereas control chow fed animals did not. Both implant groups had significant increases in stomach weights in contrast to sham implant groups, but the increase was much less in the cafeteria diet group. The fasting plasma levels of the gastrointestinal hormones, gastrin and pancreatic polypeptide, and oxytocin (a marker of vagal afferent function) were measured by radioimmunoassay. Cafeteria fed sham or implanted animals had significantly higher fasting levels of plasma oxytocin and gastrin, and significantly lower plasma levels of pancreatic polypeptide than the chow fed groups. These studies demonstrate that the gastric implant has more effect on weight in overweight animals on a palatable mixed diet, perhaps related to both mechanical and neural factors.

Topics: Animals; Body Weight; Diet; Gastrins; Male; Obesity; Organ Size; Oxytocin; Pancreatic Polypeptide; Prostheses and Implants; Rats; Rats, Inbred Strains; Stomach

Populations eating low-fat or low-fat, high-fiber diets have lower mortality rates for many cancers and coronary heart disease. The importance of nutrient composition in the lumen on absorption and on function of the gastrointestinal tract as a factor in the development of these diseases has not been studied. We investigated the plasma levels of gut-CNS peptide hormones in lean and obese Dutch women fed a high-fat meal and administered cholecystokinin (CCK). After a high-fat meal the increase in plasma CCK was similar in lean and obese women. CCK administration significantly decreased insulin release in lean and obese women, decreased glucagon release in obese women, but caused a rapid increase in plasma glucagon in lean women. Although the CCK response was similar to a fat meal in lean and obese women, differences in the control of peptide hormone release occurred in response to fat meals and CCK administration.

Topics: beta-Endorphin; Cholecystokinin; Cholesterol; Coronary Disease; Diet; Diet, Vegetarian; Dietary Fiber; Female; Gastrins; Glucagon; Humans; Insulin; Lipids; Middle Aged; Neoplasms; Obesity; Risk Factors

Topics: Administration, Oral; Adolescent; Child; Female; Gastrins; Glucagon; Glucose; Glucose Tolerance Test; Humans; Injections, Intravenous; Insulin; Male; Obesity

Topics: Animals; Cholecystokinin; Esophagus; Gastric Acid; Gastric Emptying; Gastrins; Humans; Intestine, Small; Obesity; Stomach

Topics: Adult; Diet, Reducing; Female; Gastrins; Glucagon; Humans; Male; Middle Aged; Obesity; Pancreatic Polypeptide

The influence of morbid obesity and of gastric surgery operation in circulating peptide hormone concentrations was studied in 26 patients. Plasma hormone levels were determined in the fasting state and after a standardized test meal before and six to nine months after gastric surgery. Before surgery fasting and postprandial blood glucose and hormone levels did not significantly differ in morbidly obese subjects from those in obese or normal subjects, except that in morbidly obese subjects, postprandial gastrin concentration remained at peak levels and did not return to fasting levels 120 minutes after the test meal. An average weight loss of 92 lb following the gastric surgery operation was accompanied by a decrease of fasting glucose and insulin levels and a decreased postprandial insulin response. There were no significant differences in plasma levels of pancreatic glucagon, of pancreatic polypeptide in the basal state, or of pancreatic glucagon after the test meal between the preoperative and postoperative groups. As compared to preoperative values, fasting gastrin levels decreased after surgery, the postprandial release of gastrin was virtually absent, and that of pancreatic polypeptide reduced. The significance of altered postprandial pancreatic polypeptide response and of the reversal of prolonged postprandial hypergastrinemia to a state of low circulating gastrin levels following gastric surgery on gastrointestinal secretion and mucosa remain to be determined.

Topics: Adult; Blood Glucose; Fasting; Female; Gastrins; Glucagon; Humans; Insulin; Male; Middle Aged; Obesity; Pancreatic Hormones; Pancreatic Polypeptide; Stomach

A series of variables involved in glucose handling were monitored before and after gastric bypass operation for morbid obesity. Blood glucose, insulin, C-peptide, gastric inhibitory polypeptide (GIP), pancreatic polypeptide (PP), and gastrin were measured basally and after an oral glucose load. Blood glucose, insulin, C-peptide, and PP were also measured after an intravenous glucose load. Adrenocortical function was evaluated by measuring plasma cortisol and urinary excretion of 17-hydroxy-corticosteroids and 17-ketosteroids. Nine subjects were examined before and 3 and 12 months after operation. Glucose tolerance improved postoperatively concomitant with decreased basal levels of C-peptide and insulin, increased hepatic insulin extraction, and evidence of reduced adrenocortical function. Parallel with reduced insulin resistance, support for an increase in both insulin secretion and removal was obtained postoperatively. It is concluded that the considerable endocrine abnormalities seen in morbid obesity can be normalized after gastric bypass operation and weight reduction.

Topics: Adult; Blood Glucose; C-Peptide; Female; Gastric Inhibitory Polypeptide; Gastrins; Glucose Tolerance Test; Humans; Hydrocortisone; Insulin; Male; Middle Aged; Obesity; Pancreatic Polypeptide; Stomach

The CCK- and secretin stimulated pancreatic volume, bicarbonate and enzyme secretion was investigated before and during fasting for 20 days in 12 obese subjects. Pancreatic function tests were performed at the start of the fasting period and on the 10th and 20th day. In an additional and comparable group of 8 obese patients plasma concentrations of cholecystokinin (CCK), gastrin and insulin as well as metabolic parameters (bicarbonate, beta-OH-butyrate and free fatty acids) have been measured before and during total fasting. During three weeks of total fasting the average overweight of the patients undergoing pancreatic function tests was reduced from 49 to 31% (-11.5 +/- 1,5 kg). A significant reduction of volume, bicarbonate, trypsin and amylase secretion occurred already after 10 days of total fasting. After 20 days these parameters were further significantly reduced compared to the 10th day. All mentioned parameters were found at the lower limit of the normal range at the end of the fasting period at 20 days. The only exception being lipase secretion; the decrease of this enzyme was not significant at the 5% level. No significant reduction of basal plasma concentrations could be observed for CCK and gastrin during the course of total fasting. The plasma insulin levels were significantly reduced after 7 days whereas at 10 and 20 days insulin concentration was not significantly lowered compared to day 1. A small but significant decrease in the blood bicarbonate concentration could be observed after 7 days of fasting which remained constant up to the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 3-Hydroxybutyric Acid; Adult; Amylases; Bicarbonates; Cholecystokinin; Fasting; Fatty Acids, Nonesterified; Female; Gastrins; Gastrointestinal Hormones; Humans; Hydroxybutyrates; Insulin; Male; Middle Aged; Obesity; Pancreatic Function Tests

Gastrin/CCK immunoreactivity appears to be widely distributed throughout the mammalian CNS, being most abundant in the cerebral cortex [Vanderhaeghen et al. 1975; Straus et al. 1977; Beinfeld et al. 1981]. Besides its putative role as a co-transmitter in dopaminergic neurotransmission [Hökfelt et al. 1980], cholecystokinin is apparently involved in the central regulation of appetite and satiety [Gibbs et al. 1973; Antin et al. 1975; Parret and Batt 1980; Smith 1980; Smith and Gibbs 1981] Furthermore, it has been shown that the brain concentration of the peptide is decreased in genetically obese mice as compared to non-obese animals [Strauss and Yalow 1979]. The sand rat (Psammomys obesus) is a desert rodent which tends to become diabetic when it is fed with normocaloric diet and restricted in movement [Haines et al. 1965; Hahn et al. 1971]. However, the usefulness of this animal as a paradigm of diabetes is now being revised, since because in its typical expression this metabolic dysfunction appears to be an obesity syndrome [Rice and Robertson 1980]. Therefore, it seems to be necessary to study the distribution of gastrin/CCK-immunoreactive nerve cells in the brain of normal and diabetic (obese) sand rats to get further information about mechanism underlying the development of this form of diabetes.

Topics: Animals; Arvicolinae; Cell Count; Cerebral Cortex; Cholecystokinin; Diabetes Mellitus; Gastrins; Immunoenzyme Techniques; Neurons; Obesity; Rabbits

23 obese and 17 control subjects were studied after ingestion of a heavy breakfast, and 11 obese and 11 control subjects were studied after ingestion of a mixed liquid test meal. Five subjects from the latter group were also studied two and six weeks after a jejuno-ileal bypass operation and the remaining six subjects from this group were studied twelve weeks after a stapled gastric partitioning. No significant differences in fasting or postprandial serum gastrin levels were found between the obese and the lean subjects, neither when studied with the breakfast meal nor when studied with the mixed liquid test meal. After the jejuno-ileal bypass operation the serum gastrin levels were not significantly different from the preoperative ones, whereas both the fasting and the postprandial serum gastrin levels were significantly augmented after the stapled gastric partitioning procedure. The group operated on with the latter method was also studied with an insulin test before and after the operation. Similar to that seen after ingestion of the mixed liquid test meal, the serum gastrin levels after the insulin-induced hypoglycemia were significantly higher postoperatively.

Topics: Adult; Aged; Body Weight; Fasting; Female; Food; Gastrins; Humans; Ileum; Jejunum; Male; Middle Aged; Obesity; Somatotypes; Time Factors

Fasting and meal-stimulated serum gastrin and glucose levels were measured in 11 patients before and 3 months after gastroplasty for morbid obesity. Overall blood glucose levels were significantly reduced after surgery (P less than 0.05), whereas the response to a meal was not influenced to any significant degree (P greater than 0.10). The fasting serum gastrin level was not significantly influenced by gastroplasty (P greater than 0.10). Postprandial serum gastrin increased significantly independent of gastroplasty (P less than 0.001). The presence of a marginally significant (0.10 greater than P greater than 0.05) interaction between postprandial gastrin levels and operation raises the possibility that gastroplasty additionally increases the postprandial serum gastrin level.

Topics: Adult; Blood Glucose; Female; Food; Gastrins; Humans; Middle Aged; Obesity; Stomach

Because rapid gastric emptying and a shortened satiety period might contribute to development of obesity, this study compared gastric emptying of acaloric liquid, gastric acid production, and plasma levels of gastrin and pepsinogen I (PG I) and II (PG II) among obese and nonobese Pima Indians. Rates of fractional gastric emptying and of gastric acid secretion were similar in the two groups, basally and after an acaloric liquid meal. Basal and postprandial plasma gastrin levels did not differ significantly in obese and nonobese Pimas , but peak betazole-stimulated gastric acid output was greater in the obese group, except when normalized by body weight. The plasma PG I and PG II concentrations and PG I/PG II ratio did not differ significantly between the two groups, but the PG I/PG II ratio had a positive correlation with peak acid output. No correlation was found between fractional gastric emptying rate and degree of obesity. We conclude that an increased gastric emptying rate for liquid does not contribute to the pathogenesis of obesity in Pima Indians.

Topics: Adolescent; Adult; Arizona; Betazole; Eating; Female; Gastric Acid; Gastric Emptying; Gastrins; Humans; Indians, North American; Male; Obesity; Pepsinogens; Stomach

Twenty-six patients who were more than 35 per cent above their ideal weight were examined before the introduction of a weight reduction programme. At the end of a three-month period, seven patients had lost more than 10 per cent of their body weight. These patients had significantly lower triglyceride levels, fasting gastric inhibitory polypeptide levels (GIP) and prolactin levels. Fasting vasoactive intestinal polypeptide levels (VIP) before commencing diet were raised in six of the 19 patients who subsequently did not lose weight whereas the seven patients who lost weight had normal VIP levels (X2 = 3.07, P less than 0.05). Patients with high VIP levels had higher triglyceride levels, higher mean C-terminal glucagon-like immunoreactivity (C-GLI) and higher post glucose infusion secretin levels. There was a significant correlation between triglycerides and VIP. The significance of abnormally high VIP levels in obesity and the inability of these patients to lose weight is discussed.

Topics: Adult; Cholesterol; Female; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Insulin; Lipids; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Male; Obesity; Secretin; Triglycerides; Vasoactive Intestinal Peptide

Basal plasma gastrin levels were significantly higher in obese rats induced by ventromedial hypothalamic lesions (VMH rats) than in sham-operated controls. Gastrin secretion in response to insulin hypoglycemia and a liquid diet load was higher in VMH rats than in controls. The antral gastrin concentration was also elevated in VMH rats. Pair-fed rats with VMH lesions showed increased gastrin secretion as did the non-pair-fed group. These results show that gastrointestinal hormone secretions as well as pancreatic endocrine function are abnormal in obese rats with VMH lesions. Increased gastrin secretion is probably induced by factors other then hyperphagia, such as disturbance of the autonomic nervous system due to the VMH lesions.

Topics: Animals; Blood Glucose; Gastrins; Humans; Hyperphagia; Insulin; Insulin Secretion; Male; Obesity; Rats; Rats, Inbred Strains; Vagus Nerve; Ventromedial Hypothalamic Nucleus

To elucidate the relation of noninsulin-dependent (type II) diabetes mellitus to plasma levels of gastrin, pepsinogen I, and pepsinogen II, gastric acid secretion, and gastric emptying, we studied diabetic and nondiabetic obese Pima Indian subjects. Fasting and postprandial plasma gastrin concentrations were significantly higher (P less than 0.02) in diabetic than in nondiabetic subjects, but gastric acid outputs basally, after an acaloric liquid meal, and in response to betazole were similar in the two groups. Plasma pepsinogen I and pepsinogen II levels were also similar in both groups. A significant negative relation (r = -0.84; P less than 0.01) was found between basal gastrin levels and gastric acid production in nondiabetic Indians, but not in diabetic Pimas. The fractional gastric emptying rate of an acaloric liquid meal was significantly decreased in diabetic Pimas (P less than 0.01); and at least one test showing abnormal vagal function, as estimated by the Valsalva maneuver, heart rate changes between deep expiration and inspiration, and postural hypotension, was found in every diabetic subject. These findings suggest that hypergastrinemia in type II diabetes is not related to hypochlorhydria, but, instead, results from autonomic dysfunction with slow gastric emptying.

Topics: Adult; Autonomic Nervous System; Diabetes Mellitus; Female; Gastric Acid; Gastric Emptying; Gastrins; Humans; Male; Middle Aged; Obesity; Peripheral Nerves; Vagus Nerve

Topics: Animals; Disease Models, Animal; Equipment Design; Foreign Bodies; Gastrins; Hypertrophy; Male; Obesity; Rats; Stomach; Stomach Diseases

The aim of the study was to determine the basal and meal stimulated plasma gastrin and pancreatic polypeptide levels in six morbidly obese patients before and after partial gastric transection (gastroplasty), an operation which results in the distention of the stomach with a small volume of food. The partial gastric transection involved the creation of a proximal gastric pouch of approximately 100 ml, with a 1.2 cm diameter lumen between the proximal and distal gastric pouch. Basal gastrin and pancreatic polypeptide were not altered by the operation. The magnitude of the pancreatic polypeptide response to the mean was significantly depressed, although the time course was not changed. Inhibition of pancreatic secretion is thought to be a physiological function of pancreatic polypeptide, hence its decreased release warrants further investigation in relation to the effect of partial gastric transection on pancreatic function.

Topics: Adult; Female; Food; Gastrins; Humans; Obesity; Pancreatic Polypeptide; Stomach; Time Factors

The response of serum gastric inhibitory polypeptide (GIP), serum gastrin, and blood glucose to a mixed liquid test meal with a low glucose load was measured in seven controls, in each of five patients after B II resection and proximal duodenopancreatectomy (PDP), and in three patients after jejunoileal bypass. The gastrin and glucose levels behaved as expected. However, in contrast to previously published data with higher glucose loads the integrated GIP response was slightly decreased after BII resection and significantly decreased not only after jejunoileal bypass but also after PDP. Subsequently we studied postprandial GIP release after test meals containing a low and a high glucose load in each of three controls and three patients after PDP. The results confirm a discrepant behavior of GIP release in dependence on the glucose content of the test meal after PDP compared to the controls. The hypothesis is discussed that these results reflect a special dose-effect relationship between glucose and GIP release in man.

Topics: Adult; Duodenum; Female; Gastrectomy; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucose; Humans; Ileum; Jejunum; Male; Middle Aged; Obesity; Pancreatectomy

Topics: Adult; Diabetes Mellitus; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Obesity

Fasting, meal-stimulated, and insulin-hypoglycemia-stimulated serum gastrin levels were measured before and 3 and 12 months after gastric bypass surgery in nine obese patients. The basal gastrin concentration was unaffected by the operation. After a meal both serum gastrin and blood glucose levels were significantly increased before the operation (p less than 0.002), whereas there was no significant gastrin release in response to food 3 and 12 months after the operation. Insulin hypoglycemia did not elicit any gastrin response either before or after gastric bypass surgery, even though considerable hypoglycemia was obtained. It is concluded that this lack of gastrin release after food and insulin hypoglycemia postoperatively may in part explain the rare development of peptic ulcer in patients after extensive gastric exclusion.

Topics: Eating; Fasting; Female; Gastrins; Humans; Hypoglycemia; Insulin; Male; Obesity; Stimulation, Chemical; Stomach; Time Factors

Levels of gastrin-cholecystokinin-like immunoreactivity were measured in three brain regions (cortex, diencephalon, brainstem) and the pituitary gland in groups of genetically obese Zucker rats and their non-obese littermates. The obese animals had significantly increased body weights and significantly lowered brain weights. However, levels of gastrin-cholecystokinin-like immunoreactivity were not different between the two groups in any of the regions measured. These results contrast with a recent report [11] in which ob/ob mice were found to have decreased levels of cholecystokinin in their brains.

Topics: Animals; Body Weight; Brain Chemistry; Brain Stem; Cerebral Cortex; Cholecystokinin; Diencephalon; Gastrins; Male; Obesity; Organ Size; Pituitary Gland; Radioimmunoassay; Rats; Rats, Inbred Strains; Species Specificity; Tissue Distribution

Biliopancreatic bypass for obesity entails a 2/3 distal gastrectomy with Roux-en-Y reconstruction, small bowel being transected at its midpoint and the enteroenterostomy placed 50 cm proximal to the ileocecal valve. Plasma fasting and meal-stimulated gastrin concentrations were measured by radioimmunoassay in 13 nonobese healthy volunteers, 13 pre-surgery obese patients, 11 patients within two months, 12 patients between four and twelve months and 7 patients between fifteen and twenty months after operation. There were no significant differences in fasting and meal-stimulated peak plasma gastrin levels between obese group and the control group and between any of the postoperative groups and the preoperative group. The 15-20 month post-surgery group mean fasting value was lower than in the other groups, whilst the mean peak value was unchanged. Integrated gastrin response was significantly higher in this group than in the preoperative group.

Topics: Biliary Tract Surgical Procedures; Gastrins; Humans; Jejunum; Obesity; Pancreas; Radioimmunoassay

Topics: Child; Female; Gastrins; Humans; Insulin; Male; Obesity

Topics: Adult; Body Weight; Fasting; Female; Gastrins; Humans; Male; Middle Aged; Obesity

Topics: Brain; Celiac Disease; Digestive System Physiological Phenomena; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Obesity; Pancreas; Pancreatic Neoplasms; Pancreatic Polypeptide; Secretin; Somatostatin; Substance P

Topics: Body Weight; Diet, Reducing; Epinephrine; Gastrins; Humans; Ileum; Jejunum; Obesity

Topics: Eating; Fasting; Gastrins; Humans; Jejunum; Obesity; Stomach

Nine patients were studied 1.5--3 years after jejuno-ileostomy for obesity by an intravenous glucose infusion technique designed to imitate blood glucose concentrations after glucose ingestion. Whereas serum insulin and gastrin concentrations were normal, blood glucose concentrations were significantly depressed compared to preoperative levels as well as to levels in matched normal subjects. Thus, in the fasting state mean concentrations (+/- S.E.M.) of blood glucose, serum insulin and gastrin in the patients were, respectively, 3.3 +/- 0.2 mmol/l, 95 +/- 22 pmol/l and 38 +/- 4 pmol/l. The corresponding concentrations in the matched normals were 4.3 +/- 0.2 mmol/l, 70 +/- 18 pmol/l and 39 +/- 6 pmol/l. The glucose concentrations in the patients were low in all situations, i.e. in the fasting state, after oral glucose ingestion and during the intravenous glucose infusion. The results indicate that jejuno-ileostomy in obesity greatly facilitates peripheral glucose disposal. The mechanism behind this phenomenon is not yet known.

Topics: Adult; Blood Glucose; Female; Gastrins; Humans; Ileostomy; Insulin; Jejunum; Male; Obesity

Gastrointestinal anatomy and function has been studied prospectively in 12 patients undergoing jejunoileal bypass surgery in order to investigate the adaptive response of the intestinal mucosa. The total thickness of the jejunal mucosa did not change after surgery, but the crypts became relatively deeper, suggesting a more rapid turnover of gastrointestinal cells. The absorption of oxalate was depressed in the immediate postoperative period but had improved toward preoperative levels by 6 months. Vitamin B12 absorption also declined postoperatively, and increased thereafter in the patients with an end-to-end jejunoileostomy, but showed a much smaller recovery in the group with an end-to-side anastomosis. The cholesterol concentration (lithogenicity) of the duodenal bile rose by 30% in the first 3 weeks after surgery, but had returned to preoperative levels by 6 months. The segmental absorption of glucose across the jejunum declined after surgery. Caloric intake also declined, whether measured as the quantity of food that patients elected to eat over a 24-hr period, or as the quantity of a liquid lunch which they consumed over a 20-min period. The level of basal gastric acid was increased postoperatively but the maximal output after histamine stimulation was not. The gastrin response to a standard liquid meal was also significantly increased after surgery. Enteroglucagon secretion showed an increase in 3 weeks and a further increase by 6 months after intestinal bypass surgery. The significance of these changes to intestinal adaptations is discussed.

Topics: Bile Acids and Salts; Cholesterol; Duodenum; Energy Intake; Gastric Juice; Gastrins; Glucagon; Glucose; Humans; Ileum; Intestinal Absorption; Intestinal Mucosa; Intestine, Small; Jejunum; Obesity; Oxalates; Phospholipids; Vitamin B 12

A patient in whom Cushing syndrome had been diagnosed at the age of 23 was found 14 years later to have subclinical diabetes mellitus, subcutaneous calcified fat tissue necroses, and hypergastrinemia suggesting Zollinger-Ellison syndrome. Histopathologic investigation revealed pancreatic adenomatosis of the glucagon producing A2-cells with accompanying B-cell hyperplasia, and hyperplasia of the adrenal cortex. The origin of the increased serum gastrin concentration in this patient is not yet known. The significance of A2-cell proliferation in Zollinger-Ellison syndrome and and in multiple endocrine adenomatosis is discussed.

Topics: Adipose Tissue; Adrenal Cortex; Adrenal Glands; Adult; Calcinosis; Cholecystectomy; Cushing Syndrome; Diabetes Complications; Gastrins; Glucagon; Humans; Hyperplasia; Islets of Langerhans; Male; Multiple Endocrine Neoplasia; Necrosis; Obesity; Pancreas; Zollinger-Ellison Syndrome

Topics: Gastric Juice; Gastrins; Humans; Ileum; Jejunum; Obesity

In a retrospective study the basal and food-stimulated serum concentrations of gastrin and gastric secretion of acid were studied in 28 patients following three types of intestinal shunt operation for obesity. In each type 48 cm of functioning small intestine was preserved, but the ratio between functioning jejunum and ileum was different. The basal and stimulated concentrations of gastrin in serum were significantly higher in patients with the shortest jejunum in function. There was no difference in the gastric acid output. The study suggests that gastrin participates in evoking the gastric hypersecretion of acid which follows massive bowel resection or bypass. Deprivation of a hormonal inhibitory substance from the upper jejunum may be responsible for the increased serum gastrin concentration.

Topics: Adult; Female; Food; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Ileostomy; Intestine, Small; Jejunum; Male; Obesity

Gastric bypass as a 90 per cent gastric exclusion operation was used in 393 patients with massive obesity to limit food intake. Stomal ulcer has occurred in 1.8 per cent of such patients or one ulcer per 140 man years of observation. The studies of indwelling fundic pH and of gastric acid secretion from the excluded stomach indicate that acid secretion is reduced after gastric bypass but that the acid, unbuffered by food in the excluded stomach, results in a lowered gastrin secretion after a meal. Thus, gastric bypass in inhibitory to acid secretion in most morbidly obese patients who do not have known acid peptic disease.

Topics: Achlorhydria; Analysis of Variance; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Gastroenterostomy; Humans; Obesity; Peptic Ulcer; Stomach Ulcer

In animals massive resection of the small intestine is followed by increased gastric acid secretion and an increase in serum gastrin levels. Whether hypersecretion occurs in man after intestinal resections or intestinal bypass is unclear, but an increase in fasting gastrin levels has been reported after intestinal resection. In this series a significant increase in basal gastric acid secretion and fasting serum gastrin levels has been demonstrated after intestinal bypass. However, none of the patients developed peptic ulcer or clinical symptoms of hypersecretion after the bypass operation. Whether the increase in basal secretion and the serum gastrin concentration are interrelated or of any clinical importance is uncertain.

Topics: Adult; Female; Follow-Up Studies; Gastric Juice; Gastrins; Humans; Ileostomy; Intestine, Small; Jejunum; Male; Middle Aged; Obesity

Topics: Eating; Gastrins; Humans; Ileum; Intestine, Small; Jejunum; Obesity

Jejunolieal bypass (JIB) patients provide a unique opportunity to study the relationship between small bowel loss and gastric secretory function. Preoperatively, and approximately one year postoperatively, measurements of gastric secretion were taken in 37 patients who underwent JIB for massive obesity. Basal acid output increased by 0.52 plus or minus 0.35 mEq/hr (P greater than.2), and peak stimulated acid output increased by 1.99 plus or minus 0.96 mEq/30 min (P smaller than .05). A separate group of 26 postoperative and 17 preoperative (control) JIB patients had fasting serum gastrin levels measured by radioimmunoassay. Postoperative patients had levels of 37 plus or minus 5 pg/ml, and control patients had levels of 36 plus or minus 4 pg/ml (P greater than .5). We conclude that following JIB for obesity, there is no significant change in basal acid secretion or in serum gastrin. There is a small, but statistically significant, increase in peak stimulated acid output. We currently find no clinical correlation with this change.

Topics: Fasting; Gastric Juice; Gastrins; Humans; Ileum; Intestine, Small; Jejunum; Obesity

Topics: Adrenalectomy; Adult; Age Factors; Aged; Diabetes Mellitus; Female; Gastrectomy; Gastrins; Gastrointestinal Diseases; Humans; Hypophysectomy; Liver Diseases; Male; Middle Aged; Obesity; Pituitary Diseases; Radioimmunoassay; Sex Factors; Stomach Neoplasms; Thyroid Diseases

Topics: Animals; Cholecystokinin; Gastrins; Gastrointestinal Hormones; Hyperglycemia; In Vitro Techniques; Insulin; Insulin Secretion; Islets of Langerhans; Obesity; Secretin; Secretory Rate

Topics: Animals; Blood Glucose; Gastrins; Glucose; Glucose Tolerance Test; Guinea Pigs; Humans; Immune Sera; Insulin; Iodine Radioisotopes; Islets of Langerhans; Obesity; Radioimmunoassay

Topics: Adolescent; Adult; Aged; Chromatography, Gel; Crohn Disease; Eating; Fasting; Female; Gastrins; Humans; Ileum; Iodine Radioisotopes; Jejunum; Male; Middle Aged; Obesity; Syndrome

Topics: Feeding Behavior; Gastrins; Humans; Obesity; Time Factors

Topics: Animals; Columbidae; Depression, Chemical; Gastrins; Hyperglycemia; In Vitro Techniques; Insulin; Insulin Secretion; Islets of Langerhans; Male; Mice; Obesity; Pancreatic Extracts