gastrins and Hyperglycemia

Topics: Atropine; Cimetidine; Digestion; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Hyperglycemia; Indomethacin; Insulin; Pancreas; Somatostatin; Sympathetic Nervous System; Vagotomy

Topics: Female; Follicle Stimulating Hormone; Gastrins; Glucagon; Gonadotropin-Releasing Hormone; Humans; Hyperglycemia; Hyperthyroidism; Hypothalamus; Hypothyroidism; Insulin; Luteinizing Hormone; Male; Menopause; Pituitary Gland, Anterior; Somatostatin; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Topics: Animals; Dogs; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Hyperglycemia; Islets of Langerhans; Pancreas; Pancreatitis; Peptic Ulcer; Secretin

Topics: Age Factors; Anemia, Pernicious; Antigen-Antibody Reactions; Antigens, Neoplasm; Cholecystokinin; Cross Reactions; Digestive System Physiological Phenomena; Duodenal Ulcer; Gastric Mucosa; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagon; Hepatitis B Antigens; Hormones; Humans; Hyperglycemia; Insulin; Methods; Radioimmunoassay; Secretin; Zollinger-Ellison Syndrome

Recent studies suggest that proton pump inhibitor treatment may increase insulin secretion and improve glucose metabolism in type 2 diabetes. In a randomised double-blind prospective placebo-controlled 2 × 2 factorial study, we examined the effect of esomeprazole on insulin secretion, HbA(1c) and cardiovascular risk factors in type 2 diabetes.. Forty-one patients with type 2 diabetes using dietary control or oral glucose-lowering treatment were randomised to receive add-on esomeprazole 40 mg (n = 20) or placebo (n = 21) for 12 weeks. Randomisation was carried out prior to inclusion on the basis of a computer-generated random-number list. The allocation sequence was concealed in sealed envelopes from the researcher enrolling and assessing participants. The study was undertaken at Steno Diabetes Center, Gentofte, Denmark. The primary outcome was change in AUC for insulin levels during a meal test. Secondary outcomes were the levels of HbA(1c) and biochemical markers of cardiovascular risk, including lipids, coagulation factors, inflammation markers, markers of endothelial function and 24 h ambulatory BP measurements.. Forty-one participants were analysed. In the esomeprazole-treated group the AUC for insulin did not change (before vs after treatment: 28,049 ± 17,659 vs 27,270 ± 32,004 pmol/l × min (p = 0.838). In the placebo group AUC for insulin decreased from 27,392 ± 14,348 pmol/l × min to 22,938 ± 11,936 pmol/l × min (p = 0.002). Esomeprazole treatment (n = 20) caused a ninefold increase in the AUC for gastrin. HbA(1c) increased from 7.0 ± 0.6% (53 ± 5 mmol/mol) to 7.3 ± 0.8% (56 ± 6 mmol/mol) in the esomeprazole-treated group and from 7.0 ± 0.6% (53 ± 5 mmol/mol) to 7.4 ± 0.8% (57 ± 6 mmol/mol) in the placebo group (n = 21) (p for difference in change >0.05). Except for BP, there were no differences between the groups in the markers of cardiovascular risk (p > 0.05). Monitoring of 24 h ambulatory BP showed a significant decrease in daytime systolic BP, daytime diastolic BP and 24 h diastolic BP in the placebo group (p < 0.05). No change in BP was seen in the patients treated with esomeprazole.. Treatment with esomeprazole over 12 weeks did not improve insulin secretion, glycaemic control or cardiovascular disease biomarkers in patients with type 2 diabetes.

Topics: Aged; Biomarkers; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases; Combined Modality Therapy; Denmark; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Esomeprazole; Gastrins; Glycated Hemoglobin; Humans; Hyperglycemia; Hypertension; Insulin; Insulin Secretion; Male; Middle Aged; Placebo Effect; Proton Pump Inhibitors; Risk Factors; Yogurt

Recent studies have pointed to the role of plasma glucose in the regulation of gastrointestinal function.. We have investigated the effect of acute hyperglycaemia on gastric acid secretion and pancreatic polypeptide (PP) release. Gastric acid output was measured under basal conditions and in response to intravenous infusion of gastrin-17 in two doses: 5 pmol kg-1 h for 60 min and 15 pmol kg-1 h for another 60 min. Seven healthy subjects were studied during normoglycaemia and during acute hyperglycaemia at 15 mmol L-1. Acid output was measured by continuous aspiration using phenol red as recovery marker. Plasma PP levels were determined at regular intervals.. Gastrin infusion at 5 pmol kg-1 h significantly (P < 0.05) increased acid output both during normoglycaemia and during hyperglycaemia. Gastrin infusion at 15 pmol kg-1 h further and significantly (P < 0.05) increased the acid output during both experiments. Hyperglycaemia significantly (P < 0. 05) reduced basal acid output (2.5 +/- 0.9 vs. 6.3 +/- 1.9 mmol h-1), low-dose gastrin stimulated acid output (6.5 +/- 1.7 vs. 13.0 +/- 1. 8 mmol h-1) and high-dose gastrin stimulated acid output (11.7 +/- 3. 0 vs. 19.4 +/- 3.0 mmol h-1) compared with normoglycaemia. Plasma PP levels were not stimulated by gastrin-17 infusion and were significantly (P < 0.05) reduced during hyperglycaemia.. (a) Basal and gastrin-17-stimulated gastric acid secretion are reduced during hyperglycaemia; (b) infusion of gastrin-17 to physiological post-prandial levels does not affect plasma PP levels; (c) plasma PP levels are reduced during hyperglycaemia, suggesting vagal-cholinergic inhibition of gastric acid secretion during hyperglycaemia.

Topics: Adult; Blood Glucose; Gastric Acid; Gastrins; Humans; Hyperglycemia; Male; Pancreatic Polypeptide; Vagus Nerve

Intravenous amino acids (IVAAs) are able to stimulate gastric acid secretion. We investigated the effect of concomitant intravenous infusion of glucose, leading to hyperglycemia, on gastric acid secretion induced by IVAAs. Seven healthy volunteers were studied twice, once during normoglycemia and once during acute hyperglycemia with blood glucose concentrations stabilized at approximately 15 mmol/L. Amino acids were infused intravenously at the rate of 10 g/h for 180 min. Acid output was measured by continuous aspiration using a recovery markers. Serum gastrin and plasma pancreatic polypeptide (PP) concentrations were determined at regular intervals. IVAAs significantly stimulated acid output compared with basal values (2.3 +/- 0.2 and 1.4 +/- 0.4 mmol/15 min, respectively, P < 0.05), release of gastrin, and PP during normoglycemia. Hyperglycemia completely inhibited (P < 0.05) IVAA-induced gastric acid output and significantly inhibited (P < 0.05) release of gastrin and PP. We conclude that IVAAs stimulate gastric acid secretion, and gastrin and PP release; acute hyperglycemia reduces IVAA-stimulated acid output, and gastrin and PP release; and circulating nutrients influence gastric acid and gastrointestinal hormone secretion.

Topics: Adult; Amino Acids; Blood Glucose; Female; Gastric Acid; Gastric Mucosa; Gastrins; Glucose; Humans; Hyperglycemia; Infusions, Intravenous; Male; Pancreatic Polypeptide

The incidence of esophageal adenocarcinoma (EAC) is increasing, but factors contributing to malignant progression of its precursor lesion, Barrett's esophagus (BE), have not been defined. Hypergastrinemia caused by long-term use of proton pump inhibitors (PPIs), has been suggested as one possible risk factor. The gastrin receptor, CCK2R, is expressed in the cardia and upregulated in BE, suggesting the involvement of the gastrin-CCK2R pathway in progression. In the L2-IL-1β mouse model, Barrett's-like esophagus arises from the gastric cardia. Therefore, we aimed to analyze the effect of hypergastrinemia on CCK2R+ progenitor cells in L2-IL-1β mice.. L2-IL-1β mice were mated with hypergastrinemic (INS-GAS) mice or treated with PPIs to examine the effect of hypergastrinemia in BE progression. CCK2R-CreERT crossed with L2-IL-1β mice were used to analyze the lineage progenitor potential of CCK2R+ cells. Cardia glands were cultured in vitro, and the effect of gastrin treatment analyzed. L2-IL-1β mice were treated with a CCK2R antagonist YF476 as a potential chemopreventive drug.. Hypergastrinemia resulted in increased proliferation and expansion of Barrett's-like esophagus. Lineage tracing experiments revealed that CCK2R+ cells are long-lived progenitors that can give rise to such lesions under chronic inflammation. Gastrin stimulated organoid growth in cardia culture, while CCK2R inhibition prevented Barrett's-like esophagus and dysplasia.. Our data suggest a progression model for BE to EAC in which CCK2R+ progenitor cells, stimulated by hypergastrinemia, proliferate to give rise to metaplasia and dysplasia. Hypergastrinemia can result from PPI use, and the effects of hypergastrinemia in human BE should be studied further.

Topics: Animals; Barrett Esophagus; Biomarkers; Disease Models, Animal; Disease Progression; Gastrins; Gene Expression Regulation; Hyperglycemia; Immunohistochemistry; Metaplasia; Mice; Mice, Transgenic; Myoblasts, Cardiac; Phenotype; Receptor, Cholecystokinin B

We previously reported that long-term administration of a low dose of gastrin and epidermal growth factor (GE) augments β-cell neogenesis in late-stage diabetic autoimmune mice after eliminating insulitis by induction of mixed chimerism. However, the source of β-cell neogenesis is still unknown. SRY (sex-determining region Y)-box 9(+) (Sox9(+)) ductal cells in the adult pancreas are clonogenic and can give rise to insulin-producing β cells in an in vitro culture. Whether Sox9(+) ductal cells in the adult pancreas can give rise to β cells in vivo remains controversial. Here, using lineage-tracing with genetic labeling of Insulin- or Sox9-expressing cells, we show that hyperglycemia (>300 mg/dL) is required for inducing Sox9(+) ductal cell differentiation into insulin-producing β cells, and medium hyperglycemia (300-450 mg/dL) in combination with long-term administration of low-dose GE synergistically augments differentiation and is associated with normalization of blood glucose in nonautoimmune diabetic C57BL/6 mice. Short-term administration of high-dose GE cannot augment differentiation, although it can augment preexisting β-cell replication. These results indicate that medium hyperglycemia combined with long-term administration of low-dose GE represents one way to induce Sox9(+) ductal cell differentiation into β cells in adult mice.

Topics: Animals; Blood Glucose; Cell Differentiation; Culture Media; Diabetes Mellitus, Experimental; Epidermal Growth Factor; Gastrins; Hyperglycemia; Insulin-Secreting Cells; Kinetics; Mice, Inbred C57BL; Pancreatic Ducts; SOX9 Transcription Factor

The aim of this study was to investigate whether combined epidermal growth factor (EGF) and gastrin can correct the hyperglycemia induced by streptozotocin (STZ) in rats and to determine the involvement of the transcription factor pancreatic and duodenal homeobox 1 (PDX1) in this process.. Rat diabetes was induced by intraperitoneal injection of STZ. The mRNA and protein levels of insulin and PDX1 were determined by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. Serum levels of C-peptide and insulin were analyzed using radioimmunoassay kits.. The combined administration of EGF and gastrin efficiently reversed the hyperglycemia induced by STZ. Elevated insulin concentration was detected in diabetic rats treated with EGF plus gastrin. The authors also found that both insulin and PDX1 expression were reduced in STZ-treated rats. Interestingly, the combination treatment also significantly enhanced the mRNA levels of insulin and PDX1, and that of their protein products.. Therapy with EGF plus gastrin corrected hyperglycemia and maintained insulin content in STZ-induced diabetic rats via up-regulation of PDX1 expression, suggesting that this combination treatment may provide a valuable approach for pancreatic islet neogenesis in vivo.

Topics: Animals; C-Peptide; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Drug Combinations; Epidermal Growth Factor; Gastrins; Homeodomain Proteins; Humans; Hyperglycemia; Injections, Subcutaneous; Insulin; Islets of Langerhans; Male; Radioimmunoassay; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Trans-Activators

β-Cell mass reduction is a central aspect in the development of type 1 and type 2 diabetes, and substitution or regeneration of the lost β-cells is a potentially curative treatment of diabetes. To study the effects of gastrin on β-cell mass in rats with 95% pancreatectomy (95%-Px), a model of pancreatic regeneration, rats underwent 95% Px or sham Px and were treated with [15 leu] gastrin-17 (Px+G and S+G) or vehicle (Px+V and S+V) for 15 d. In 95% Px rats, gastrin treatment reduced hyperglycemia (280 ± 52 mg vs. 436 ± 51 mg/dl, P < 0.05), and increased β-cell mass (1.15 ± 0.15 mg)) compared with vehicle-treated rats (0.67 ± 0.15 mg, P < 0.05). Gastrin treatment induced β-cell regeneration by enhancing β-cell neogenesis (increased number of extraislet β-cells in Px+G: 0.42 ± 0.05 cells/mm(2) vs. Px+V: 0.27 ± 0.07 cells/mm(2), P < 0.05, and pancreatic and duodenal homeobox 1 expression in ductal cells of Px+G: 1.21 ± 0.38% vs. Px+V: 0.23 ± 0.10%, P < 0.05) and replication (Px+G: 1.65 ± 0.26% vs. S+V: 0.64 ± 0.14%; P < 0.05). In addition, reduced β-cell apoptosis contributed to the increased β-cell mass in gastrin-treated rats (Px+G: 0.07 ± 0.02%, Px+V: 0.23 ± 0.05%; P < 0.05). Gastrin action on β-cell regeneration and survival increased β-cell mass and improved glucose tolerance in 95% Px rats, supporting a potential role of gastrin in the treatment of diabetes.

Topics: Animals; Apoptosis; Cell Count; Cell Proliferation; Cell Size; Diabetes Mellitus; DNA Replication; Gastrins; Glucose Intolerance; Homeodomain Proteins; Hyperglycemia; Hypoglycemic Agents; Islets of Langerhans; Male; Organ Size; Pancreas; Pancreatectomy; Rats; Rats, Sprague-Dawley; Receptor, Cholecystokinin A; Regeneration; Trans-Activators

Gastrin has been implicated in islet growth/neogenesis, and proton pump inhibitors (PPIs) have been shown to increase endogenous gastrin levels in animals and humans. Therefore, we investigated the effect of PPIs in a model of type 2 diabetes, Psammomys obesus.. P. obesus (morning blood glucose [mBG] 16.9 +/- 0.6 mmol/l) were treated with vehicle or different doses (1-15 mg/kg) of lansoprazole for 17 days.. Treatment with lansoprazole resulted in up to ninefold dose-dependent increases in endogenous gastrin levels (p < 0.05 for 10 mg/kg lansoprazole vs vehicle). There was a significant reduction in mBG levels in all animals in the high-dose lansoprazole groups during the 17 day treatment period, whereas there was no significant improvement in mBG in animals in the vehicle groups. The mBG at end of study was 18.2 +/- 2.1, 8.7 +/- 2.2 (p < 0.01), and 6.1 +/- 2.3 (p < 0.001) mmol/l for vehicle and lansoprazole 10 and 15 mg/kg, respectively. The animals treated with 15 mg/kg lansoprazole, compared with vehicle, had a 2.3-fold increase in the intensity of insulin staining in beta cells (p=0.0002) and 50% higher beta cell mass (p=0.04).. The PPI lansoprazole had significant glucose-lowering effects in an animal model of type 2 diabetes, an effect that is most likely mediated through an increase in endogenous gastrin levels.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Analysis of Variance; Animals; Blood Glucose; Diabetes Mellitus, Type 2; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors; Female; Gastrins; Gerbillinae; Hyperglycemia; Immunohistochemistry; Insulin; Insulin-Secreting Cells; Lansoprazole; Male; Proton Pump Inhibitors

We explored the hypothesis that meal-regulated release of insulin from gastric G cells can be used for gene therapy for diabetes. We generated transgenic mice in which the coding sequence of human insulin has been knocked into the mouse gastrin gene. Insulin was localized specifically to antral G cells of G-InsKi mice by double immunofluorescence staining using antibodies against insulin and gastrin. Insulin extracted from antral stomach of G-InsKi mice decreased blood glucose upon injection into streptozotocin-diabetic mice. Intragastric administration of peptone, a known potent luminal stimulant of gastrin secretion, induced an increase in circulating levels of transgenic human insulin from 10.7 +/- 2 to 23.3 +/- 4 pm in G-InsKi mice. Although G cell-produced insulin decreased blood glucose in G-InsKi mice, it did not cause toxic hypoglycemia. Proton pump inhibitors, pharmacological agents that increase gastrin output, caused a further increase in the circulating levels of gastric insulin (41.5 +/- 2 pm). G cell-produced insulin was released into circulation in response to the same meal-associated stimuli that control release of gastrin. The most striking aspect of the results presented here is that in the presence of the G-InsKi allele, Ins2(Akita/+) mice exhibited a marked prolongation of life span. These results imply that G cell-derived transgenic insulin is beneficial in the amelioration of diabetes. We suggest that an efficient G cells-based insulin gene therapy can relieve diabetic patients from daily insulin injections and protect them from complications of insulin insufficiency while avoiding episodes of toxic hypoglycemia.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Eating; Gastric Mucosa; Gastrin-Secreting Cells; Gastrins; Genetic Therapy; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Mice; Mice, Inbred C57BL; Mice, Transgenic

Combination therapy with epidermal growth factor (EGF) and gastrin induces beta-cell regeneration in rodents with chemically induced diabetes. We investigated whether EGF plus gastrin could correct hyperglycemia in NOD mice with autoimmune diabetes. Combined treatment with EGF (1 mug/kg) and gastrin (3 mug/kg) for 2 weeks restored normoglycemia after diabetes onset in NOD mice, whereas EGF or gastrin alone did not. Fasting blood glucose remained normal (3.5-6.5 mmol/l) or mildly elevated (<11 mmol/l) in five of six mice (83%) for 10 weeks after EGF plus gastrin treatment was stopped, whereas all mice treated with vehicle or EGF or gastrin alone became severely hyperglycemic (12-35 mmol/l). Pancreatic beta-cell mass was increased threefold and insulin content was increased eightfold in mice treated with EGF plus gastrin compared with pretreatment values. The correction of hyperglycemia correlated significantly with increases in pancreatic beta-cell mass and insulin content. In addition, splenic cells from mice treated with EGF plus gastrin delayed diabetes induction by adoptive transfer of diabetogenic cells into immunodeficient NOD-scid mice, suggesting the induction of immunoregulatory cells in NOD mice treated with EGF plus gastrin. We conclude that a short course of combined EGF and gastrin therapy increases pancreatic beta-cell mass and reverses hyperglycemia in acutely diabetic NOD mice; the impact of this combined therapy may result from the effects of EGF and gastrin on beta-cells, immune cells, or both.

Topics: Animals; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Epidermal Growth Factor; Female; Gastrins; Hyperglycemia; Islets of Langerhans; Mice; Mice, Inbred NOD

We have examined the effect of an acute stable hyperglycemia on gastric acid secretion during the gastric phase of digestion. Gastric acid output was measured with a recovery marker (phenol red) under basal conditions and after repeated intragastric instillation of a liquid meal in seven healthy subjects on two separate occasions: during normoglycemia (serum glucose, 15 mM). Premeal gastric acid output was significantly (P < 0.05) reduced during hyperglycemia compared with during normoglycemia (2.6 +/- 1.0 vs. 5.8 +/- 1.8 mmol/h). Intragastric meal-stimulated incremental acid output during hyperglycemia was significantly (P < 0.05) reduced compared with during normoglycemia (19 +/- 4 vs. 38 +/- 9 mmol/120 min). Meal-stimulated gastrin release during hyperglycemia was significantly (P < 0.05) reduced compared with that during normoglycemia (4.9 +/- 1.3 vs. 6.6 +/- 1.6 micrograms.1(-1).120 min-1). The intragastric meal induced significant (P < 0.05) increases in pancreatic polypeptide concentrations only during normoglycemia. During hyperglycemia, recovery rates of gastric contents were significantly (P < 0.05) increased compared with during normoglycemia, both before (81 +/- 4 vs. 71 +/- 6%) and after (72 +/- 4 vs. 57 +/- 4%) meal ingestion, pointing to delayed gastric emptying of liquids during hyperglycemia. In conclusion, 1) gastric acid secretion under unstimulated conditions and during the gastric phase of digestion is reduced during hyperglycemia; 2) meal-stimulated gastrin release is significantly reduced during hyperglycemia; 3) the reduction in meal-stimulated acid output is correlated with the reduction in gastrin releases; and 4) pancreatic polypeptide secretion is significantly reduced during hyperglycemia, pointing to impaired vagal cholinergic tone.

Topics: Adult; Blood Glucose; Digestion; Female; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Hyperglycemia; Insulin; Male; Pancreatic Polypeptide; Stomach

Topics: Dumping Syndrome; Gastrins; Glucose; Humans; Hyperglycemia; Hypoglycemia; Peptic Ulcer

To examine the mechanism of the recently reported effect of an acidified intragastric test meal on insulin release and glucose homeostasis, a liver extract test meal at either pH 2 or pH 7 was instilled into the stomach of normal dogs and dogs with a chemical sympathectomy or indomethacin-induced prostaglandin deficiency, all of which had a bisected pylorus and gastric fistula. In the normal dogs the instillation of the liver meal at pH 2 elicited a significant rise in plasma glucose, glucagon and insulin levels, while in response to the meal at pH 7 only glucagon rose significantly. This was not altered in chemically sympathectomized dogs, nor during the infusion of indomethacin. In all experiments gastrin or gastric glucagon release in response to the meal at pH 2 was either lower than or similar to the response to the meal at pH 7. These data suggest that the influence of the stomach upon islet cell function and glucose homeostasis does not depend on either adrenergic innervation or the presence of prostaglandings, but rather is mediated by a yet undetermined mechanism.

Topics: Animals; Blood Glucose; Dogs; Food; Gastrins; Glucagon; Hydrogen-Ion Concentration; Hydroxydopamines; Hyperglycemia; Hyperinsulinism; Indomethacin; Liver Extracts; Prostaglandins; Prostaglandins E; Sympathetic Nervous System

The effects of hyperglycemia on pancreatic, biliary, and gastric secretory responses to meals have not been hitherto quantified in man. In the present study seven normal volunteers were fed on two occasions a 500-ml liquid test meal containing fat and protein. During one of the meals the subjects were made acutely hyperglycemic with intravenous glucose, whereas in control experiments, each subject received intravenous saline in place of glucose. A jejunal perfusion method was used to measure pancreatic outputs of trypsin and biliary outputs of bile salts for 150 min after the meal; the same method was used to quantify indirectly the amount of acid secreted by the stomach in the 150-min period. Serum gastrins were also measured basally and at intervals after the meal. Hyperglycemia suppressed serum gastrin, gastric acid production, trypsin secretion, and bile salt output in response to the test meal.

Topics: Bile Acids and Salts; Blood Glucose; Dietary Fats; Dietary Proteins; Eating; Gastric Juice; Gastrins; Glucose; Humans; Hyperglycemia; Trypsin

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

Topics: Acute Kidney Injury; Adenoma, Islet Cell; Dehydration; Diarrhea; Female; Gastrins; Humans; Hyperglycemia; Hyperinsulinism; Hypokalemia; Insulin; Insulin Secretion; Kidney Diseases; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Zollinger-Ellison Syndrome

Topics: Amides; Animals; Dogs; Gastrins; Glucagon; Hyperglycemia; Insulin; Insulin Secretion; Islets of Langerhans; Pancreas; Peptides; Propylene Glycols; Receptors, Drug; Stimulation, Chemical; Veins

The fasting serum level of gastrin was determined by radioimmunoassay in 41 normal subjects, 27 patients with duodenal ulceration, 12 patients with gastric ulceration, and 8 patients following "complete" vagotomy. The patients with duodenal ulceration had significantly higher serum levels of gastrin (1.3 +/- S.D. 0.7 ng./ml.) than normal subjects (0.4 +/- S.D. 0.3 ng./ml.), patients with gastric ulceration (0.4 +/- S.D. 0.4 ng./ml.), or post-vagotomy patients (0.15 +/- S.D. 0.2 ng./ml.).The gastrin secretion in both normal subjects and patients with duodenal ulceration was responsive to protein ingestion, but a larger incremental secretion of gastrin occurred in the latter group. Hyperglycaemia significantly suppressed the serum level of gastrin in both groups. The patients with gastric ulceration had fasting and postprandial serum gastrin levels not significantly different from normal subjects.

Topics: Dietary Proteins; Duodenal Ulcer; Fasting; Food; Gastrins; Humans; Hyperglycemia; Injections, Intravenous; Peptic Ulcer; Radioimmunoassay; Stomach Ulcer; Vagotomy

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

The effects upon islet hormone secretion of highly purified preparations of secretin and of pancreozymin-cholecystokinin and of a crude gastrin-containing extract of hog antrum have been studied in acutely operated dogs. All three preparations were shown to cause a striking increase in insulin concentration in the pancreaticoduodenal venous plasma after their rapid endoportal injection in anesthetized dogs. With each hormone preparation, the peak in insulin secretion occurred 1 minute after injection, and a rapid decline was observed immediately thereafter. Whereas secretin and gastrin failed to alter significantly the pancreaticoduodenal venous glucagon or arterial glucose concentration, pancreozymin caused a dramatic rise in pancreaticoduodenal venous glucagon concentration, which reached a peak 3 minutes after injection, and hyperglycemia was noted to occur soon thereafter. Endoportal infusion of secretin and pancreozymin for 20 minutes caused responses that were sustained but qualitatively identical to the responses noted after rapid injection of the hormones. The beta-cytotropic effect of secretin was abolished by the infusion of epinephrine. These results could not be attributed to the small degree of contamination of the enteric hormone preparations with insulin or glucagon, and it would appear that secretin, pancreozymin, and probably gastrin have insulin-releasing activity and that pancreozymin has, in addition, glucagon-releasing activity.The demonstration that these three hormones possess insulin-releasing activity suggests that there is in the gastrointestinal tract a chain of betacytotropic hormones from antrum to ileum that is capable of augmenting insulin secretion as required for disposal of substrate loads. It is suggested that the existence of this "entero-insular axis" prevents high substrate concentrations that would otherwise follow ingestion of large meals were the insular response entirely a function of arterial substrate concentration.

Topics: Adrenocorticotropic Hormone; Animals; Blood Glucose; Cholecystokinin; Dogs; Epinephrine; Gastrins; Glucagon; Growth Hormone; Hyperglycemia; Insulin; Secretin; Vasopressins