gastrins and Diabetes-Mellitus

Two major initiatives are under way to correct the beta-cell deficit of diabetes: one would generate beta-cells ex vivo that are suitable for transplantation, and the second would stimulate regeneration of beta-cells in the pancreas. Studies of ex vivo expansion suggest that beta-cells have a potential for dedifferentiation, expansion, and redifferentiation. Work with mouse and human embryonic stem (ES) cells has not yet produced cells with the phenotype of true beta-cells, but there has been recent progress in directing ES cells to endoderm. Putative islet stem/progenitor cells have been identified in mouse pancreas, and formation of new beta-cells from duct, acinar and liver cells is an active area of investigation. Peptides, including glucagon-like peptide-1/exendin-4 and the combination of epidermal growth factor and gastrin, can stimulate regeneration of beta-cells in vivo. Recent progress in the search for new sources of beta-cells has opened promising new opportunities and spawned clinical trials.

Topics: Cell Differentiation; Diabetes Mellitus; Embryo, Mammalian; Embryo, Nonmammalian; Epidermal Growth Factor; Exenatide; Gastrins; Glucagon; Glucagon-Like Peptide 1; Islets of Langerhans; Pancreas; Peptide Fragments; Peptides; Protein Precursors; Regeneration; Stem Cells; Venoms

Topics: Animals; Cell Differentiation; Cell Division; Cell Transplantation; Cells, Cultured; Diabetes Mellitus; Embryonic and Fetal Development; Endothelial Growth Factors; Gastrins; Humans; Intercellular Signaling Peptides and Proteins; Islets of Langerhans; Lymphokines; Models, Animal; Pancreas; Rats; Regeneration; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

The authors carried out a self-controlled study using 11, non-obese patients with impaired glucose tolerance. The first day an oral glucose tolerance test was performed as a control. This was repeated the next day with a simultaneous intake of 20 g natural wheat bran. On both days blood samples were taken at 30 minute intervals (for three hours period) after glucose or glucose plus bran ingestion to measure the plasma sugar, insulin, C-peptid, gastrin and glucagon levels. It has been found that: 1. With simultaneous bran intake the blood glucose levels were decreased as compared to the control values. 2. The serum insulin, and C-peptid levels were similar in both tests. 3. The glucagon response curve fell below that of the control. 4. The serum gastrin levels did not show any change following either glucose or glucose plus bran intake. It has been concluded, that the dietary fibres are able to decrease of glucagon release, beside their direct inhibitory effect on the level of sugar absorption from gastrointestinal tract.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus; Dietary Fiber; Gastrins; Glucagon; Glucose Tolerance Test; Humans; Insulin; Intestinal Absorption; Triticum

Topics: Cholecystokinin; Diabetes Mellitus; Endocrine Glands; Endocrine System Diseases; Female; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Male; Somatostatin; Thyroid Diseases

Topics: Diabetes Mellitus; Gastrins; Humans; Pancreatic Hormones; Pancreatic Neoplasms; Peptic Ulcer; Somatostatin; Vasoactive Intestinal Peptide

Information concerning GEP hormones has progressively advanced since the initial discovery of a GEP hormone, secretin, in 1902. Studies in this area flourished with the advent of radioimmunoassay, and have provided an understanding of the secretion, regulation, metabolic actions, and role in certain diseases of major GEP hormones. Measurement of GEP hormones has achieved importance in clinical medicine and allowed understanding of the pathophysiology of several clinical disorders. The decade to come should witness additional advances in this rapidly expanding field.

Topics: Chemical Phenomena; Chemistry; Cholecystokinin; Diabetes Mellitus; Diarrhea; Endocrine System Diseases; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Hypoglycemia; Motilin; Neoplasms; Neurotensin; Pancreatic Polypeptide; Peptic Ulcer; Secretin; Skin Diseases; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Topics: Adipose Tissue; Amino Acid Sequence; Animals; Diabetes Mellitus; Gastric Acid; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose; Humans; Insulin; Pancreatitis; Pepsin A; Peptide Fragments; Peptides; Proinsulin; Radioimmunoassay; Salivation; Splanchnic Circulation

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: Adenoma, Islet Cell; Chenodeoxycholic Acid; Cholecystokinin; Cholelithiasis; Dehydration; Diabetes Mellitus; Duodenal Ulcer; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Motilin; Pancreatic Neoplasms; Secretin; Syndrome; Vasoactive Intestinal Peptide; Zollinger-Ellison Syndrome

Topics: Adrenocorticotropic Hormone; Antigen-Antibody Reactions; Awards and Prizes; Brain; Diabetes Mellitus; Digestive System; Gastrins; Hepatitis B Antigens; History, 20th Century; Hormones; Humans; Insulin; Protein Precursors; Radioimmunoassay

Topics: Acromegaly; Animals; Diabetes Mellitus; Digestive System Physiological Phenomena; Gastrins; Glucagon; Growth Hormone; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Liver; Nelson Syndrome; Nervous System; Pituitary Gland; Somatostatin; Thyroid Gland

Somatostatin, under physiological conditions, is a regulator of thyroid stimulating hormone, growth hormone, pancreatic islet-cell hormones and gastrin. In pharmacological dosage, gastric acid output, splanchnic blood flow and plasma renin levels, are influenced. A possible therapeutic effect on increased growth hormone secretion, disturbances of carbohydrate metabolism, gastroenteropathies and renal hypertension, is discussed. The clinical application is limited by the short biological half-life of the substance and the unspecific action on several organs.

Topics: Acromegaly; Animals; Diabetes Mellitus; Diabetic Retinopathy; Gastric Juice; Gastrins; Growth Hormone; Humans; Hypertension; Islets of Langerhans; Pancreatitis; Renin; Somatostatin; Thyrotropin; Zollinger-Ellison Syndrome

Topics: Acromegaly; Adenoma, Islet Cell; Animals; Binding Sites; Blood Glucose; Diabetes Mellitus; Diabetic Ketoacidosis; Dose-Response Relationship, Drug; Gastrins; Glucagon; Humans; Insulin; Insulin Secretion; Secretory Rate; Somatostatin; Thyrotropin

Topics: Adrenocorticotropic Hormone; Blood Glucose; Diabetes Mellitus; Gastric Juice; Gastrins; Glucagon; Growth Hormone; Humans; Hypoglycemia; Insulin; Islets of Langerhans; Male; Organ Specificity; Pancreas; Pancreatic Neoplasms; Somatostatin; Thyrotropin; Thyrotropin-Releasing Hormone

Topics: Adenoma, Islet Cell; Animals; Diabetes Mellitus; Diarrhea; Gastrins; Glucagon; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Islets of Langerhans Transplantation; Pancreatic Hormones; Pancreatic Neoplasms; Peptic Ulcer; Somatostatin; Transplantation, Homologous

Topics: Acromegaly; Adenoma, Islet Cell; Adrenocorticotropic Hormone; Bronchial Neoplasms; Diabetes Mellitus; Gastrins; Glucagon; Growth Hormone; Humans; Hypoglycemia; Neoplasms; Pancreatic Neoplasms; Somatostatin; Thyrotropin; Zollinger-Ellison Syndrome

Topics: Animals; Diabetes Mellitus; Gastrins; Glucagon; Gonadal Steroid Hormones; Growth Hormone; Hormones; Humans; Insulin; Insulin Secretion; Somatostatin

Topics: Amino Acid Sequence; Animals; Blood Glucose; Diabetes Mellitus; Duodenum; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Glucagon; Glucose; Histamine; Humans; Insulin; Islets of Langerhans; Pentagastrin; Peptides; Swine; Triglycerides

Topics: Animals; Biogenic Amines; Carcinoid Tumor; Cholecystokinin; Chromaffin System; Diabetes Mellitus; Digestive System; Digestive System Physiological Phenomena; Gastric Juice; Gastrins; Gastrointestinal Hormones; Gastrointestinal Neoplasms; Glucagon; Humans; Insulin; Insulin Secretion; Intestines; Pancreas; Pancreatic Neoplasms; Peptic Ulcer; Secretin; Syndrome

Topics: Animals; Cholecystokinin; Diabetes Mellitus; Duodenum; Gastrins; Gastrointestinal Hormones; Glucose; Glucose Tolerance Test; Humans; In Vitro Techniques; Islets of Langerhans; Rats; Secretin; Serotonin; Tissue Extracts

Topics: Anemia, Pernicious; Animals; Diabetes Mellitus; Duodenal Ulcer; Gastric Mucosa; Gastrins; Humans; Peptic Ulcer; Rats; Secretory Rate; Stomach Ulcer

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Chlorpromazine; Circadian Rhythm; Cold Temperature; Diabetes Mellitus; Diet; Female; Gastric Juice; Gastrins; Humans; Kidney Diseases; Male; Middle Aged; Stomach Ulcer; Stress, Physiological

Topics: Animals; Arginine; Blood Glucose; Cholecystokinin; Cyclic AMP; Diabetes Mellitus; Dietary Proteins; Digestive System Physiological Phenomena; Gastrins; Glucagon; Humans; Hypoglycemia; Insulin; Insulin Secretion; Islets of Langerhans; Portal System; Postgastrectomy Syndromes; Regional Blood Flow; Secretin; Serotonin

Topics: Cholecystokinin; Diabetes Mellitus; Fatty Acids, Essential; Gastrins; Gastrointestinal Hormones; Glucagon; Glucose; Humans; Islets of Langerhans; Secretin

Topics: Amino Acids; Animals; Autonomic Nervous System; Blood Glucose; Cholecystokinin; Diabetes Mellitus; Dietary Carbohydrates; Dietary Proteins; Gastrectomy; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Glucagon; Glucose; Humans; Hypoglycemia; In Vitro Techniques; Insulin; Insulin Secretion; Intestinal Mucosa; Islets of Langerhans; Microcirculation; Portal System; Secretin

Topics: Autoantibodies; Autoimmune Diseases; Cholecystokinin; Diabetes Mellitus; Gastrins; Gastrointestinal Hormones; Glucagon; Glucose; Humans; Insulin; Secretin; Trace Elements

Abnormal gastric slow-wave frequencies have been observed in diabetic gastroparesis and are associated with impaired antral motor activity. In this study, we aimed at evaluating the effect of acupuncture on gastric slow waves in diabetic patients with symptoms suggesting gastric motor dysfunction.. Fifteen patients with type II diabetes who had had dyspeptic symptoms for more than 3 months were enrolled. Two acupuncture needles were inserted into the subjects' legs at the Zusanli points, and electrical stimulation (2-Hz pulses) was delivered for 30 min. Cutaneous electrogastrography was performed for 30 min at baseline, for 30 min during acupuncture, and for an additional 30 min after acupuncture. Serum gastrin, motilin, and human pancreatic polypeptide levels were also measured.. There was a significant increase in the percentages of normal frequency during and after acupuncture (baseline vs. acupuncture and after acupuncture 21.99 +/- 19.38% vs. 45.93 +/- 19.72 and 48.92 +/- 19.56%; p < 0.01). In addition, the percentage of tachygastric frequency was decreased significantly during and after acupuncture. The dominant frequency was also changed significantly. There was an increase of serum human pancreatic polypeptide during acupuncture (baseline vs. acupuncture 56.96 +/- 27.64 vs. 73.11 +/- 22.37 pmol/l; p < 0.05).. The results of this study revealed that electrical stimulation at the Zusanli points could increase the percentage of normal electrogastrography frequency and decrease the percentage of tachygastric frequency in diabetic patients. The data indicate that acupuncture may enhance the regularity of gastric myoelectrical activity in diabetic patients.

Topics: Acupuncture Points; Adult; Aged; Blood Glucose; Diabetes Complications; Diabetes Mellitus; Electroacupuncture; Female; Gastrins; Gastrointestinal Motility; Gastroparesis; Humans; Male; Middle Aged; Motilin; Pancreatic Polypeptide; Pilot Projects

β-Cell failure in type 2 diabetes (T2D) was recently proposed to involve dedifferentiation of β-cells and ectopic expression of other islet hormones, including somatostatin and glucagon. Here we show that gastrin, a stomach hormone typically expressed in the pancreas only during embryogenesis, is expressed in islets of diabetic rodents and humans with T2D. Although gastrin in mice is expressed in insulin

Topics: Aged; Aged, 80 and over; Animals; Basic Helix-Loop-Helix Transcription Factors; Case-Control Studies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Gastrins; Gene Expression Regulation, Developmental; Gerbillinae; Humans; Immunohistochemistry; Insulin-Secreting Cells; Islets of Langerhans; Male; Mice; Nerve Tissue Proteins; Real-Time Polymerase Chain Reaction; Somatostatin-Secreting Cells; Stem Cells

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

Topics: Animals; Diabetes Mellitus; Diabetes Mellitus, Type 1; Epidermal Growth Factor; Gastrins; Growth Substances; Humans; Islets of Langerhans; Mice; Regeneration

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

The histopathology of Fibrocalculous Pancreatic Diabetes (FCPD) has been extensively studied, but there are no reports on alteration in patterns of hormone secreting cells using immunohistochemistry in islets of FCPD patients. In this study, we report on the histopathology and immunohistochemistry of islets of FCPD patients and its possible correlation with the clinical picture. Pancreatic biopsies were carried out in six patients with FCPD at the time of surgery for abdominal pain. Routine histopathology and immunohistochemistry studies were carried out with six primary antibodies namely insulin, glucagon, pancreatic polypeptide (PP), somatostatin, vasoactive intestinal peptide and gastrin. Histopathology of the pancreas showed a spectrum of changes ranging from moderate to severe atrophy, fibrosis of the parenchyma and degeneration of the ducts. Nesidioblastosis was present in three patients. Immunohistochemical studies showed a decrease in the number of islets but some patients showed evidence of hyperplasia. There was an overall decrease in the percent of insulin cells and the positivity in the islets correlated with plasma C-peptide levels and the duration of diabetes. There was no consistent relationship with glucagon with some patients showing increased and other decreased positivity. There was a marked decrease in PP and somatostatin positivity, the significance of which is not clear. The reduction, but partial preservation of insulin positivity is consistent with the ketosis resistance shown by patients with Fibrocalculous Pancreatic Diabetes.

Topics: Adolescent; Adult; Atrophy; Biopsy; Blood Glucose; Chronic Disease; Diabetes Mellitus; Female; Gastrins; Glucagon; Humans; Hyperplasia; Immunohistochemistry; Insulin; Islets of Langerhans; Male; Middle Aged; Pancreas; Pancreatic Ducts; Pancreatic Polypeptide; Pancreatitis; Vasoactive Intestinal Peptide

The antral endocrine cells were investigated in nonobese diabetic (NOD) mice by means of immunohistochemistry, image analysis, and radioimmunoassays (RIA). As controls BALB/CJ mice of the same age and sex as the NOD mice were used. The number of gastrin- and somatostatin-immunoreactive cells was significantly decreased in both prediabetic and diabetic mice. There was no statistical difference between the NOD mice and controls regarding the serotonin-immunoreactive cells. Somatostatin levels as revealed by RIA in the antrum of both prediabetic and diabetic NOD mice were lower than those of the controls. There was no statistical difference in the level of antral gastrin between NOD mice and the controls. It was concluded that the changes in antral cells are primary to the onset of diabetes, and that the abnormalities observed in the antral cells in an animal model for diabetes type I might have relevance for the upper gastrointestinal dysfunction displayed in human diabetes.

Topics: Animals; Diabetes Mellitus; Disease Models, Animal; Enteroendocrine Cells; Female; Gastrins; Image Processing, Computer-Assisted; Immunohistochemistry; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Pyloric Antrum; Radioimmunoassay; Somatostatin

A disturbed intraduodenal milieu and pancreatic scarring in advanced chronic pancreatitis (CP) may lead to changes of gut and pancreatic hormones. In the present study, the gastroduodenal mucosal content of several regulatory peptides was determined in 8 patients with severe calcific CP and 8 healthy volunteers. In addition, hormone release into the bloodstream was estimated after intraduodenal acid/glucose stimulation in the control subjects and 8 CP patients each with or without secondary diabetes mellitus (DM), and in 8 patients with juvenile DM, so that disturbed gut hormone release could be attributed either to CP or DM. While VIP release into the circulation was similar in all participants, mucosal levels of VIP and substance P were significantly elevated in the duodenal bulb and descending duodenum of CP patients. The somatostatin content of gastroduodenal mucosa in CP was at least as high as in normals. Gastrin was significantly more abundant only in the duodenal bulb of CP patients, while plasma gastrin was normal. Duodenal CCK concentrations tended to be elevated in the duodenal bulb, but not significantly. The release of secretin seemed to be higher in type-1 diabetics than in CP patients. The mucosal pattern of GIP was nearly identical in CP patients and controls. Compatible with this finding, the GIP release did not show any peculiarities in CP with or without DM or in DM. Basal and stimulated plasma levels of motilin were abnormally high in CP. Pancreatic polypeptide plasma levels were normal in DM, but significantly reduced in CP, especially in CP with DM. Fasting PP and stimulated pancreatic enzyme outputs were linearly related.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Chronic Disease; Diabetes Mellitus; Female; Gastric Inhibitory Polypeptide; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Humans; Intestinal Mucosa; Male; Middle Aged; Motilin; Neurotensin; Pancreatic Polypeptide; Pancreatitis; Secretin; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Gastrin releasing peptide(GRP)-like immunoreactivity in human plasma was measured using radioimmunoassay of neuromedin C (NMC) in 83 healthy and 58 diseased subjects. In the healthy group, the mean value of fasting GRP-like immunoreactivity was 2.1 +/- 1.4 (mean +/- SD) pmol/L. There was a slight positive correlation between the GRP-like immunoreactivity values and aging. Postprandial serial measurements demonstrated that GRP-like immunoreactivity showed no response to a significant elevation of serum gastrin concentration. The group with chronic renal failure on hemodialysis gave the highest value, 7.1 +/- 2.1 pmol/L (p less than 0.01). There were no statistical differences between the healthy controls and groups with peptic ulcer, liver cirrhosis, diabetes mellitus or carcinomas, although some cancer patients had a marked increase in GRP-like immunoreactivity value.

Topics: Adult; Aged; Bombesin; Diabetes Mellitus; Female; Gastrin-Releasing Peptide; Gastrins; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Neoplasms; Peptic Ulcer; Peptide Fragments; Peptides; Radioimmunoassay

Topics: Animals; Diabetes Mellitus; Endocrine System Diseases; Gastrins; Heart; Hormones; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Ketone Bodies; Myocardium; Periodicity; Rats; Receptor, Insulin; Receptors, Adrenergic, beta; Receptors, Muscarinic; Somatostatin; Vasoactive Intestinal Peptide

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

It has been claimed that plasma cholecystokinin (CCK) concentrations are raised in patients with pancreatic insufficiency. We have measured plasma CCK concentrations in 32 patients with pancreatic insufficiency (22 alcoholic pancreatitis and 10 cystic fibrosis) and in 30 normal subjects by radioimmunoassays using antibodies with different specificities. Antibody 1703 binds to COOH-terminal forms of CCK containing at least 14 amino acid residues and does not cross-react with gastrins. Antibody T204 binds to all CCK-peptides containing the sulfated tyrosyl region and shows low cross-reactivity with sulfated gastrins but no binding to nonsulfated gastrins. Antibody 5135 binds to all COOH-terminal CCK-peptides and shows full cross-reactivity with gastrins. In patients with pancreatic insufficiency, plasma CCK concentrations (1.2 +/- 0.1 pmol/liter, antibody 1703; 2.0 +/- 0.2 pmol/liter, antibody T204; 12.5 +/- 1.4 pmol/liter, antibody 5135) were not significantly different from those in normal subjects (1.1 +/- 0.1 pmol/liter, antibody 1703; 2.2 +/- 0.3 pmol/liter, antibody T204; 10.5 +/- 0.9 pmol/liter, antibody 5135). Furthermore, plasma CCK concentrations in patients with pancreatic insufficiency due to alcoholic pancreatitis (1.2 +/- 0.1 pmol/liter, antibody 1703; 1.9 +/- 0.2 pmol/liter, antibody T204; 14.0 +/- 1.9 pmol/liter, antibody 5135) were not significantly different from those in patients with cystic fibrosis (1.2 +/- 0.2 pmol/liter, antibody 1703; 2.4 +/- 0.4 pmol/liter, antibody T204, 9.1 +/- 1.0 pmol/liter, antibody 5135). Cross-reactivity with gastrin accounted for almost all CCK-like-immunoreactivity measured with antibody 5135.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Alcoholism; Antibodies; Antibody Specificity; Binding Sites, Antibody; Cholecystokinin; Cross Reactions; Cystic Fibrosis; Diabetes Mellitus; Exocrine Pancreatic Insufficiency; Female; Gastrins; Humans; Male; Middle Aged; Pancreatitis; Radioimmunoassay

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

Blood gastrin, sugar, insulin and glucagon were studied after a protein meal with or without 400 mg cymethidine per os in 7 normal subjects and 14 with anacidotic adult diabetes in a reasonable state of glycometabolic compensation. The association led to a significant enhancement of gastrin after 120' and 180', plus a rise in the total integrated gastrin response. Sugar and insulin were unaffected, while glucagon was distinclty, though not signifacantly, reduced. In a discussion of the results it is suggested that the rise in gastrin after cymethidine is not solely due to a pH-dependent negative feedback, since this should have led to an earlier (30', 60') rise, but also to the slight suppression of glucagon, which is physiologically endowed with the ability to inhibit secretion.

Topics: Adult; Aged; Blood Glucose; Cimetidine; Diabetes Mellitus; Diabetic Ketoacidosis; Dietary Proteins; Female; Gastrins; Glucagon; Guanidines; Humans; Insulin; Middle Aged

Topics: Adult; Diabetes Complications; Diabetes Mellitus; Food; Gastric Emptying; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Middle Aged; Pentagastrin; Stomach; Vomiting

Many gastrointestinal structural and functional properties are known to be altered in diabetes. In this study, we investigated whether serum and tissue gastrin levels are abnormally altered in a strain of genetically diabetic mice (C57BL/KSJ). Both serum and antral gastrin concentration were found to be significantly increased 3.4- and 2-fold above normal values in diabetic mice fed ad libitum. The increase in tissue gastrin concentration is most probably due to an increase in both cellular gastrin content and G-cell number, since the latter property is increased 130% in diabetic animals. Pair feeding studies demonstrated that diabetes associated hyperphagia is not a major factor in inducing these endocrine changes, since antral and serum gastrin are still significantly elevated above normal in diabetic animals fed a restricted diet. G-cell number, however, is not significantly increased above normal values in pair fed diabetic mice. The peak serum gastrin concentration after a meal and the duration of postprandial hypergastrinemia are also significantly increased above normal in diabetic animals. Gel filtration chromatography studies indicate that the antral nucosae of normal and diabetic mice have identical molecular forms of the hormone. It is therefore concluded that antral and serum gastrin concentration are increased in genetically diabetic mice due to both dietary alterations and other, as yet undefined, factors specific for the disease, and that the resultant hypergastrinemia may contribute to some of the gastrointestinal alterations seen in diabetes.

Topics: Animals; Blood Glucose; Cell Count; Diabetes Mellitus; Enterochromaffin Cells; Female; Food; Gastrins; Male; Mice; Mice, Inbred C57BL; Molecular Conformation; Pyloric Antrum

Topics: Antigens; Diabetes Mellitus; Gastrins; Humans; Hyperthyroidism; Hypothyroidism; Insulin; Tolbutamide

Secretin releasing response to intraduodenal acid infusion was investigated in 15 cases of diseased control, 7 cases of duodenal ulcer, 5 cases of chronic pancreatitis, and 6 cases of diabetes mellitus. Plasma secretin levels in response to duodenal acidification were less in duodenal ulcer and the appearance of the maximal peak was delayed compared with that found in control. It is suggested that the secretin release was impaired in duodenal ulcer in spite of hypersecretion of gastric acids. In chronic pancreatitis, secretin releasing response to acidification was markedly impaired, in addition, inhibition of secretin release by bicarbonate was diminished due to a lack of bicarbonate flow from the pancreas. On the other hand, although the response of secretin release in diabetes mellitus was also lower compared with that in control group, the capacity of secretin response showed values in-between control subjects and chronic pancreatitis. This research was supported in part by grant from the Ministry of Education, Science and Culture in Japan.

Topics: Adolescent; Adult; Chronic Disease; Diabetes Mellitus; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Male; Middle Aged; Pancreatitis; Secretin

Serum gastrin concentrations were measured in insulin-dependent diabetics and in patients who had undergone total duodenopancreatectomy and gastrectomy. Administration of somatostatin markedly inhibited gastrin release in the diabetic patients with an intact gastrointestinal tract. This inhibitory effect of somatostatin, however, is not detectable in the group of operated patients, who display basically low plasma gastrin levels. A marked increase in the plasma gastrin level after withdrawal of somatostatin was observed in patients with a normal gastrointestinal tract. This rebound effect was only slight in the operated patients.

Topics: Diabetes Mellitus; Gastrectomy; Gastrins; Humans; Pancreatectomy; Somatostatin

Topics: Diabetes Mellitus; Gastrins; Glucagon; Humans; Insulin; Pancreas; Radioimmunoassay

We have developed a sensitive, specific and reproducible radioimmunoassay for cholecystokinin (CCK) with which basal levels of CCK of between 400-800 pg/ml have been measured in normal man, in patients with diabetes and with duodenal ulcer disease, and in normal dogs. After a meal, circulating levels of CCK rose to 1000-1200 pg/ml in human subjects. Release of CCK was more rapid in diabetic and duodenal ulcer patients than in normal subjects, but elevated postprandial levels persisted much longer in normal subjects. Patients with the Zollinger-Ellison syndrome had elevated values of cholecystokinin which rose after a meal. Lack of correlation between elevated basal levels of gastrin and CCK in patients with the Zollinger-Ellison syndrome suggest that the hypercholecystokininemia may be absolute. The disappearance half-time of exogenous CCK was about 21/2 minutes in normal subjects as well as in diabetic and duodenal ulcer patients. Studies in dogs demonstrated no uptake of basal levels of cholecystokinin by the kidney; on infusion of exogenous CCK-33, the kidney extracted 43% of the total CCK presented and 56% of the integrated CCK. We conclude that: 1) circulating basal and postprandial levels of CCK may be measured in a reproducible fashion; 2) postprandial release of CCK is more rapid in diabetic and duodenal ulcer patients than in normal man; 3) the disappearance half-time of exogenous CCK in man and dogs is about 21/2 minutes; 4) the kidney is a major site for uptake of CCK.

Topics: Animals; Cholecystokinin; Diabetes Mellitus; Dogs; Duodenal Ulcer; Food; Gastrins; Half-Life; Humans; Kidney; Radioimmunoassay; Zollinger-Ellison Syndrome

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: Diabetes Mellitus; Gastrins; Glucose Tolerance Test; Humans

Topics: Arginine; Blood Glucose; Cholecystokinin; Diabetes Mellitus; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Hypoglycemia; Insulin; Male; Radioimmunoassay; Secretin; Stimulation, Chemical

Topics: Anemia, Pernicious; Animals; Cattle; Diabetes Mellitus; Gastric Juice; Gastrins; Humans; Kidney Diseases; Rabbits; Radioimmunoassay

Topics: Adult; Animals; Biological Assay; Blood Glucose; Cholecystokinin; Diabetes Mellitus; Dogs; Gastrins; Humans; Immunoassay; Insulin; Insulin Secretion; Methods; Middle Aged; Portal Vein; Secretin; Stimulation, Chemical

Topics: Adult; Aged; Animals; Diabetes Mellitus; Female; Gastrins; Gastrointestinal Diseases; Guinea Pigs; Humans; Male; Middle Aged; Radioimmunoassay

Topics: Amino Acids; Cholecystokinin; Diabetes Mellitus; Fatty Acids, Nonesterified; Gastrins; Glucagon; Glycolysis; Humans; Insulin; Insulin Secretion; Oxygen Consumption; Secretin

Topics: Adult; Biopsy; Diabetes Mellitus; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Histamine; Histological Techniques; Humans; Injections, Intravenous; Peptides; Stimulation, Chemical; Stomach; Stomach Ulcer

Topics: Biopsy; Diabetes Mellitus; Gastric Juice; Gastric Mucosa; Gastrins; Gastritis; Histamine; Humans; Peptic Ulcer

Topics: Animals; Blood Glucose; Cholecystokinin; Diabetes Mellitus; Dogs; Fatty Acids, Nonesterified; Gastrins; Gastrointestinal Hormones; Glucagon; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Rabbits; Secretin; Serotonin; Stimulation, Chemical