gastrins and Hypoglycemia

Topics: Allylamine; Animals; Blood Glucose; Bromocriptine; Cardiovascular Diseases; Colesevelam Hydrochloride; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Dipeptidyl-Peptidase IV Inhibitors; Gastrins; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Islet Amyloid Polypeptide; Leptin; Metformin; Sodium-Glucose Transporter 1; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Sulfonylurea Compounds; Thiazolidinediones; United States

Diabetes mellitus is a complex chronic disease associated with an absolute insulin deficiency in type 1 diabetes (T1D) and a progressive deterioration of β-cell function in type 2 diabetes (T2D). T2D pathophysiology has numerous defects including incretin deficiency/resistance. Gastrin has demonstrated to be an islet growth factor (like glucagon-like peptide-1, epidermal growth factor, transforming growth factor-α,…) and be able to restore a functional β-cell mass in diabetic animals. This hormone is likely to stimulate insulin secretion during an ordinary protein-rich meal, this is, to have an incretin-like effect. Proton pump inhibitors (PPIs) can raise serum gastrin concentration significantly and therefore, affect to glucose metabolism through promoting β-cell regeneration/expansion and also enhancing insulin secretion. The present paper aims to review studies concerning the effect of PPIs on glucose metabolism. Several research groups have recently explored the potential role of this class of drugs on glycemic control, mainly in T2D. The results show antidiabetic properties for the PPIs with a global glucose-lowering power around 0.6-0.7 % points of HbA1c, but the level of evidence for the available literature is still not high. If these data start to become demonstrated in the ongoing clinical trials, PPIs could become a new antidiabetic agent with a good and safe profile for T2D and even useful for T1D, particularly in the area of islet transplantation to preserve β-cell mass.

Topics: Animals; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Enterochromaffin-like Cells; Gastric Emptying; Gastrin-Secreting Cells; Gastrins; Gastrointestinal Agents; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Secretion; Insulin-Secreting Cells; Parietal Cells, Gastric; Proton Pump Inhibitors; Somatostatin; Somatostatin-Secreting Cells

Pancreatic neuroendocrine tumors (PNETs) are rare neoplasms representing <5% of all pancreatic malignancies with an estimated incidence of 1-1.5 cases/100,000. PNETs are broadly classified as either functional or nonfunctional. Functional PNETs include insulinomas, gastrinomas, vasoactive intestinal peptideomas, glucagonomas, and somatostatinomas. The clinical manifestations associated with these tumors are the result of excessive hormonal secretion and action. The functional nature of these tumors makes pancreatic hormone testing critical not only for initial diagnosis but also for follow-up, because they are important tumor markers. Nonfunctional PNETs typically remain clinically silent until a substantial mass effect occurs. Although the majority of PNETs occur sporadically, it is important to recognize that these tumors may be associated with a variety of familial syndromes and in many cases genetic testing of PNET patients is warranted. This article familiarizes the reader with the clinical presentation and the biochemical, radiologic, and genetic testing indicated for diagnosis and follow-up of patients with PNET.

Topics: Gastrinoma; Gastrins; Glucagon; Glucagonoma; Hormones; Humans; Hypoglycemia; Insulinoma; Neuroendocrine Tumors; Pancreatic Neoplasms; Somatostatinoma; Vasoactive Intestinal Peptide; Vipoma

As beta-adrenergic blockers grow increasingly popular for the therapy of a wide variety of disorders, it becomes increasingly important to appreciate the spectrum of physiologic effects on the gastrointestinal system and the potential hazards associated with use of these agents. This review details the effects of the beta-adrenergic blocking agents on the gastrointestinal tract.

Topics: Adrenergic beta-Antagonists; Animals; Bile Ducts; Digestive System; Drug Interactions; Gastrectomy; Gastric Acid; Gastrins; Gastrointestinal Motility; Humans; Hypoglycemia; Intestinal Absorption; Intestinal Mucosa; Pancreas; Peritonitis; Receptors, Adrenergic

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: Achlorhydria; Acromegaly; Adenoma; Adenoma, Islet Cell; Adolescent; Adult; Aged; Calcium; Cushing Syndrome; Diarrhea; Female; Gastric Acid; Gastrins; Glucagon; Humans; Hyperinsulinism; Hyperparathyroidism; Hypoglycemia; Hypokalemia; Male; Middle Aged; Neoplasms, Multiple Primary; Pancreatic Polypeptide; Pancreatitis; Parathyroid Glands; Parathyroid Neoplasms; Pituitary Neoplasms; Syndrome; Thyroid Diseases; Zollinger-Ellison Syndrome

Topics: Animals; Catecholamines; Circadian Rhythm; Dogs; Duodenal Ulcer; Gastrins; Humans; Hypoglycemia; Physical Exertion; Receptors, Adrenergic, beta; Smoking; Vagotomy

Topics: Animals; Deoxyglucose; Dogs; Duodenal Ulcer; Eating; Electric Stimulation; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Humans; Hypoglycemia; Insulin; Pepsin A; Vagotomy; Vagus Nerve

Topics: Animals; Dumping Syndrome; Gastrectomy; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Humans; Hypoglycemia; Insulin; Insulin Secretion; Postoperative Complications; Vagotomy

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: 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: 5-Hydroxytryptophan; Adrenocorticotropic Hormone; Chorionic Gonadotropin; Gastrins; Hormones, Ectopic; Humans; Hypercalcemia; Hypoglycemia; Neoplasms; Parathyroid Hormone; Precancerous Conditions; Thyrotropin; Vasopressins

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: 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: Adenoma, Islet Cell; Diarrhea; Digestive System; Fasting; Gastrins; Glucagon; Glucose; Glucose Tolerance Test; Humans; Hypoglycemia; Hypokalemia; Leucine; Pancreatic Neoplasms; Tolbutamide; Zollinger-Ellison Syndrome

Gastric acid output, blood-glucose, serum-gastrin and psychomotor-performance were measured in four healthy subjects one hour before and two hours after the intravenous injection of (a) 2ml saline, (b) 0.2 U/kg b.w. insulin, (c) 0.1 mg/kg b.w. bromazepam. Each subject underwent one experiment of each type. The study was layed out as a Latin-square and analysed accordingly. Gastric acid secretion was measured by means of intragastric titration and a telemetering capsule; blood-glucose and serum-gastrin levels as well as psychomotor performance as a measure of vigilance were determined in 15-minute-intervals. In the saline series (a), none of the four parameters showed any systematic variation. In series (b), a bimodal response of acid output to insulin, initial inhibition and subsequent stimulation was observed in all subjects. Serum-gastrin levels showed only a slight and transient increase in the first thirty minutes. Psychomotor performance decreased markedly with progressing hypoglycemia, and increased when glucose levels rose again. In the bromazepan series (c), acid output and psychomotor performance decreased and, after the first hour, increased almost parallely, while glucose and gastrin levels remained unchanged. In series (d), an additive effect of insulin and bromazepam occurred: acid output and psychomotor performance were lower than after insulin alone; peak acid secretion, maximal hypoglycemia and peak of serum-gastrin were shifted to the right. It is concluded that the lowered basal as well as insulin-stimulated acid secretion after bromazepam is due to the central effect of the drug, and that this effect is mediated to the gastric glands directly via autonomic nervous pathways without involving a release of endogenous gastrin.

Topics: Adult; Anti-Anxiety Agents; Arousal; Blood Glucose; Bromazepam; Female; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Male; Motor Skills; Time Factors

Topics: Blood Glucose; Clinical Trials as Topic; Depression, Chemical; Duodenal Ulcer; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Hypoglycemia; Insulin; Placebos; Propranolol; Stimulation, Chemical; Stomach Ulcer; Vagotomy

Both cholecystokinin (CCK)-A and CCK-B receptors are expressed in the pancreas, and exogenous gastrin administration stimulates glucagon secretion from human islets. Although gastrin action has been linked to islet neogenesis, transdifferentiation, and beta-cell regeneration, an essential physiologic role(s) for gastrin in the pancreas has not been established.. We examined glucose homeostasis, glucagon gene expression, glucagon secretion, and islet mass in mice with a targeted gastrin gene disruption.. Gastrin -/- mice exhibit fasting hypoglycemia and significantly reduced glycemic excursion following glucose challenge. Insulin sensitivity was normal and levels of circulating insulin and insulin messenger RNA transcripts were appropriately reduced in gastrin -/- mice. In contrast, levels of circulating glucagon and pancreatic glucagon messenger RNA transcripts were not up-regulated in hypoglycemic gastrin -/- mice. Furthermore, the glucagon response to epinephrine in isolated perifused islets was moderately impaired in gastrin -/- versus gastrin +/+ islets (40% reduction; P < 0.01, gastrin +/+ vs. gastrin -/- mice). Moreover, the glucagon response but not the epinephrine response to hypoglycemia was significantly attenuated in gastrin -/- compared with gastrin +/+ mice (P < 0.05). Despite gastrin expression in the developing fetal pancreas, beta-cell area, islet topography, and the islet proliferative response to experimental injury were normal in gastrin -/- mice.. These findings show an essential physiologic role for gastrin in glucose homeostasis; however, the gastrin gene is not essential for murine islet development or the adaptive islet proliferative response to beta-cell injury.

Topics: Animals; Fasting; Female; Gastrins; Glucagon; Glucose; Homeostasis; Hypoglycemia; Insulin; Islets of Langerhans; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Receptor, Cholecystokinin B; Receptors, Cholecystokinin

Topics: Aged; Duodenal Ulcer; Fasting; Female; Gastrins; Humans; Hypoglycemia; Neoplasm Proteins; Thyrotropin; Zollinger-Ellison Syndrome

This study examined whether or not changes in plasma concentrations of motilin and other gastrointestinal hormones known to affect gastric motility are associated with the accelerated gastric emptying seen during hypoglycaemia. While studying gastric emptying by scintigraphy in eight healthy subjects, the plasma concentrations of glucagon, adrenaline, motilin, gastrin, neuropeptide Y and somatostatin were measured during normoglycaemia and hypoglycaemia with simultaneous infusion of either atropine or saline. Blood glucose concentrations were checked by an insulin-glucose clamp. The plasma levels of glucagon and adrenaline increased markedly during both hypoglycaemic examinations compared with normoglycaemia. Neither motilin nor any of the other hormones displayed considerable changes during hypoglycaemia with and without atropine compared with normoglycaemia. No further information about the mechanisms behind the accelerated gastric emptying rate during hypoglycaemia was obtained by analysing motilin and the other gastrointestinal hormones.

Topics: Adult; Blood Glucose; Epinephrine; Gastric Emptying; Gastrins; Glucagon; Glucose Clamp Technique; Humans; Hypoglycemia; Male; Motilin; Neuropeptide Y; Neuropeptides; Somatostatin

Gastrin is expressed in the gastric antrum and in fetal pancreatic islets but not in adult islets. We have now identified the hepatobiliary tract as another, previously unknown, potential site of gastrin gene expression. Two human gastrin simian virus 40 large tumor antigen (SV40 T antigen) fusion genes containing 1.5 kb of 5' flanking sequence and 10.5 kb that included 5.5 kb upstream, 1.5 kb downstream, and the entire transcribed region were used to generate transgenic mice. Analysis of several transgenic lines, derived from both fusion genes, revealed development of transmissible hepatobiliary tract tumors and pancreatic islet cell tumors. Analysis of each of the tumor cells demonstrates expression of SV40 T antigen but no expression of gastrin. Of the two fusion genes, only the 10.5-kb sequence induces hyperplasia of gastrin-producing cells in the antrum. Analysis of these cells demonstrates expression of SV40 T antigen and gastrin, suggesting that the 10.5-kb sequence is sufficient for gastrin cell hyperplasia in the antrum. These data raise the possibility that gastrin is transiently expressed in the hepatobiliary tract.

Topics: Adenoma, Islet Cell; Animals; Antigens, Viral, Tumor; Biliary Tract Neoplasms; Gastric Mucosa; Gastrins; Hyperplasia; Hypoglycemia; Mice; Mice, Nude; Mice, Transgenic; Pyloric Antrum; Recombinant Fusion Proteins; Simian virus 40

We previously established pluripotent transformed rat islet cell lines, MSL-cells, of which certain clones have been used to study processes of islet beta-cell maturation, including the transcriptional activation of the insulin gene induced by in vivo passage. Thus, successive sc transplantation in NEDH rats resulted in stable hypoglycemic insulinoma tumor lines, such as MSL-G2-IN. Occasionally, hypoglycemia as well as severe weight loss were observed in the early tumor passages of MSL-G and the subclone, NHI-5B, which carry the transfected neomycin and human insulin genes as unique clonal markers. By selective transplantation, it was possible to segregate stable anorectic normoglycemic tumor lines, MSL-G-AN and NHI-5B-AN, from both clones. These tumors cause an abrupt onset of anorexia when they reach a size of 400-500 mg (< 0.3% of total body weight), and the observed weight loss parallels that of starved rats until death results from cachexia. After tumor resection, animals immediately resume normal feeding behavior. Comparative studies of hormone release and mRNA content in anorectic lines, MSL-G-AN and NHI-5B-AN, vs. those in the insulinoma line, MSL-G2-IN, revealed selective glucagon gene expression in both of the anorectic tumors, whereas insulin and islet amyloid polypeptide gene expression were confined to the insulinoma. Both tumor phenotypes produced cholecystokinin and gastrin in variable small amounts, making it unlikely that these hormones contribute to the anorectic phenotype. Tumor necrosis factor (cachectin) was not produced by any of the tumors. Proglucagon was processed as in the fetal islet to products representative of both pancreatic alpha-cell and intestinal L-cell phenotypes, with glucagon and Glp-1 (7-36)amide as the major extractable products. In contrast to the administration of cholecystokinin, neither glucagon, Glp-1 (7-36)amide, nor their combination, affected feeding behavior in fasted mice, suggesting the presence of a hitherto unidentified anorectic substance released from the glucagonoma. We conclude 1) that glucagonomas and insulinomas can be derived from a common clonal origin of pluripotent MSL cells, thus supporting the existence of a cell lineage relationship between islet alpha- and beta-cell during ontogeny; and 2) that our glucagonomas release an anorexigenic substance(s) of unknown nature that causes a severe weight loss comparable to that reported in animals carrying tumor necrosis factor-producing experimental

Topics: Adenoma, Islet Cell; Animals; Anorexia; Base Sequence; Blotting, Northern; Cholecystokinin; Eating; Gastrins; Gene Expression; Glucagon; Hormones; Hypoglycemia; Molecular Sequence Data; Neoplasm Transplantation; Pancreatic Neoplasms; Protein Precursors; Rats; Tumor Cells, Cultured; Weight Loss

The insulinoma is the most common pancreas tumour with endocrine activity, with more than 2,000 cases being described in the literature worldwide. The first successful extirpation was performed by Graham in 1928. Clinical appearance is characterized by severe paroxysmal hypoglycaemia together with inadequately increased serum insulin levels. Surgery is indicated in such situations because of limited effectiveness of medicamentous therapy. Surgical approach and long-time results are discussed in this paper, with reference being made to 13 cases of the authors.

Topics: Adenoma, Islet Cell; Adult; C-Peptide; Female; Follow-Up Studies; Gastrins; Glucose Tolerance Test; Humans; Hypoglycemia; Insulin; Insulinoma; Male; Neoplasm Recurrence, Local; Pancreatectomy; Pancreatic Neoplasms; Postoperative Complications; Reoperation

High basal gastrin levels in pure autonomic failure could result from peripheral vagus nerve involvement, whereas the increased response during hypoglycaemia may reflect adrenergic supersensitivity. A reduced gastrin increment in multiple system atrophy was found following insulin-hypoglycaemia and is consistent with decreased gastrin release secondary to diminished central sympathetic nervous system activation in the absence of peripheral denervation supersensitivity.

Topics: Adult; Aged; Autonomic Nervous System Diseases; Blood Glucose; Epinephrine; Female; Gastrins; Humans; Hypoglycemia; Hypotension, Orthostatic; Insulin; Male; Middle Aged; Norepinephrine; Stomach; Sympathetic Nervous System

Plasma gastrin and somatostatin responses to ingestion of a solid meal, to insulin hypoglycemia, and to intravenous infusion of gastrin-releasing peptide were measured in 4 conscious dogs with and without bilateral cryogenic blockade of the cervical vagus nerves. Vagal cooling to -2 degrees C abolished meal-stimulated rises in plasma gastrin and somatostatin. Atropine did not modify the gastrin response to cooling but bethanechol reduced the magnitude of inhibition to 37% +/- 9% without influencing plasma somatostatin. Gastrin-releasing peptide elevated postprandial plasma gastrin during vagal blockade to levels comparable to those with the vagus intact but did not alter the nadir plasma somatostatin response. The plasma gastrin and somatostatin rises associated with insulin hypoglycemia were similarly inhibited by cooling to -2 degrees C. Cooling to 12 degrees C, which selectively blocks vagal inhibitory pathways, had no effect on meal-stimulated gastrin release and partially decreased the plasma gastrin response to insulin hypoglycemia. Thus, gastrin release by food and by insulin hypoglycemia is mediated by a vagal nonmuscarinic excitatory pathway that is independent of changes in circulating plasma somatostatin but may include participation by the candidate neurotransmitter gastrin-releasing peptide.

Topics: Animals; Atropine; Bethanechol; Bethanechol Compounds; Cold Temperature; Dogs; Food; Gastrin-Releasing Peptide; Gastrins; Gastrointestinal Hormones; Hypoglycemia; Neural Pathways; Peptides; Receptors, Muscarinic; Somatostatin; Vagus Nerve

Topics: Adult; Duodenal Ulcer; Gastrins; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Insulin Secretion; Male; Pancreatic Diseases; Vagotomy

Postvagotomy hypergastrinemia may result from withdrawal of tonic vagal inhibitory mechanism(s) or from G-cell hyperplasia secondary to diminished acid secretion. Early development of hypergastrinemia, after vagotomy, would favor the first mechanism, whereas delayed development would favor the second. We sought to distinguish between these two mechanisms and to determine whether alterations in somatostatin release might mediate postvagotomy hypergastrinemia. We measured plasma concentrations of gastrin and somatostatinlike immunoreactivity basally and in response to meal (pH controlled at 5.5) and to insulin hypoglycemia before and after truncal vagotomy in 11 dogs. Basal and postprandial hypergastrinemia were established within 24 and 48 h after vagotomy, respectively. Basal and meal-stimulated plasma somatostatinlike immunoreactivity concentrations were unaltered by vagotomy, although insulin hypoglycemia-induced rises in plasma somatostatinlike immunoreactivity were abolished by vagotomy. Our data suggest that neither G-cell hyperplasia nor alterations in somatostatin release explain postvagotomy hypergastrinemia in the dog. The observations support the hypothesis that postvagotomy hypergastrinemia results from the withdrawal of a tonic vagal inhibitory mechanism of gastrin release that is independent of somatostatin. Whether the tonic vagal inhibition of gastrin is direct or indirect is unknown.

Topics: Animals; Dogs; Dose-Response Relationship, Drug; Gastric Acid; Gastric Fistula; Gastrins; Histamine; Hypoglycemia; Insulin; Postoperative Period; Somatostatin; Time Factors; Vagotomy

Plasma gastrin and gastric acid responses to intravenous injection of insulin (0.2 IU/kg) were measured in 8 patients with Chagas' disease, which is known to be associated with extensive reduction of the intramural neurons of the digestive tract, and in 6 control subjects. All subjects developed hunger, sweating and tachycardia, and exhibited less than 50 mg/dl venous blood glucose. Plasma gastrin responses in Chagas' disease patients (median: 3.60 nmol L-1 min-1; range: 1:12 to 10.60 nmol L-1 min-1) were significantly higher than for control subjects (median: 0.52 nmol L-1 min-1; range: 0.25 to 1.09 nmol L-1 min-1). Gastric acid output was significantly lower in Chagas' disease patients (median: 3.5 mmol/h; range: 2.1 to 13.6 mmol/h) than in controls (median: 30.3 mmol/h; range: 7.3 to 38.2 mmol/h). These data show that chagasic patients have abnormally high gastrin release and low gastric acid secretion in response to insulin, and thus indicate that loss of intrinsic innervation of the stomach does not abolish the gastrin response to insulin hypoglycemia.

Topics: Adult; Blood Glucose; Chagas Disease; Female; Gastric Acid; Gastrins; Humans; Hypoglycemia; Insulin; Male; Middle Aged

The relation between gastric acid secretion and plasma concentrations of adrenaline, noradrenaline, dopamine and gastrin was investigated in normal volunteers, adrenalectomized subjects and patients with duodenal ulcer (DU) during digestion and in response to insulin and modified sham feeding (MSF). Basal plasma noradrenaline concentrations were significantly higher in DU patients than in normals whereas basal plasma adrenaline and dopamine concentrations were low in both groups. Basal acid output was similar in the two groups. Insulin markedly increased plasma adrenaline in controls but had no discernible effect in adrenalectomized subjects. Still, there was no difference between acid secretion in the two groups. Insulin, but not MSF, caused a marked increase in plasma catecholamine concentrations in DU patients whereas the acid responses were the same. The significantly increased plasma noradrenaline concentration in DU patients was normalized 6 weeks after highly selective vagotomy but tended to return to the preoperative value 1 year postoperatively. Our results suggest that endogenously released adrenaline might affect gastric function only when present in extremely high plasma concentrations. The pathophysiological role of noradrenaline in DU disease remains obscure.

Topics: Catecholamines; Chronic Disease; Duodenal Ulcer; Eating; Gastric Acid; Gastric Mucosa; Gastrins; Histamine H2 Antagonists; Humans; Hypoglycemia; Insulin; Vagotomy

To study whether specific beta-adrenergic mechanisms contribute to the hypoglycaemic activation of gastrin and gastric acid secretion, the effects of racemic and dextroisomer propranolol (0.1 mg/kg, intravenously) were studied during insulin tests (0.2 IU/kg) in 13 persons. dl-Propranolol inhibited the gastrin response to hypoglycaemia markedly and more than the insignificant alteration observed after d-propranolol. Gastric acid response to hypoglycaemia was significantly reduced by dl-propranolol and not by d-propranolol. The findings demonstrate that non-beta-adrenergic effects of propranolol on the stomach are minor and that specific beta-adrenergic mechanisms are directly or indirectly involved in the hypoglycaemic stimulation of the stomach.

Topics: Adult; Blood Glucose; Female; Gastric Acid; Gastrins; Humans; Hypoglycemia; Insulin; Male; Middle Aged; Propranolol; Stereoisomerism

Administration of 6 hydroxydopamine (6 OHDA) causes selective acute degeneration of the adrenergic nerve terminals, that is a reversible chemical sympathectomy. The effect of this drug was studied on the insulin stimulated gastric secretion. Insulin stimulated (0.15-0.4 IU/kg) gastric acid and pepsin output and serum gastrin was measured before and after 6 OHDA treatment (40 mg/kg) in gastric fistula dogs. Chemical sympathectomy resulted in a highly significant increase in acid and pepsin secretion. However, the hypoglycemic gastrin release was unaltered except the peak response, which showed a significant reduction. These data confirm earlier observations, that the sympathetic innervation of the stomach has an inhibitory effect on gastric secretion in the dog. Furthermore it seems that the adrenergic fibres in the vagus nerve might have some moduling effect on the insulin induced gastrin release.

Topics: Animals; Blood Glucose; Dogs; Gastric Acid; Gastric Juice; Gastrins; Hypoglycemia; Insulin; Pepsin A; Sympathectomy, Chemical

The gastric acid response to insulin hypoglycemia represents an effect of several stimulatory and inhibitory mechanisms. In the intact stomach the direct vagal excitation of the acid secreting glands is the predominant mechanism. After vagotomy, however, the balance between the stimulatory and inhibitory mechanisms is unpredictable. Some stimulatory and inhibitory mechanisms are non-vagal, and may after vagotomy result in a false conception of remaining vagal fibers and complete vagotomy, respectively. Sham feeding may be a safer and more reliable test of completeness of vagotomy. A study of the spontaneous variation of basal acid secretion over several hours after vagotomy in 22 patients showed in 15-min samples a maximal range of 0.49 and 0.65 mmol with a P value of 0.05 and 0.01, respectively. A higher range may thus indicate a true acid response to a given stimulus. In 3 patients with an acid response to sham feeding but no acid response to insulin in a dose of 0.2 IU/kg after vagotomy, a repeated test with a lower dose of insulin resulted in an unequivocal acid response. In 4 patients with no acid response to sham feeding and a substantial acid response to insulin after vagotomy, the acid response to insulin was abolished after pretreatment with an adrenergic blocker. The insulin test may thus give false negative and positive information about the completeness of vagotomy.

Topics: Animals; Biomechanical Phenomena; Dogs; Eating; Evaluation Studies as Topic; Gastric Acid; Gastrins; Humans; Hypoglycemia; Insulin; Outcome and Process Assessment, Health Care; Physical Stimulation; Vagotomy

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

Topics: Animals; Blood Glucose; Dose-Response Relationship, Drug; Gastric Acid; Gastric Mucosa; Gastrins; Glucose; Histamine; Histamine Release; Histidine Decarboxylase; Hypoglycemia; Insulin; Male; Pentagastrin; Rats; Rats, Inbred Strains; Vagus Nerve

A method is described for complete isolation of the stomach in the dog with vagal innervation intact. This involves esophagostomy, double mucosal closure of the pylorus and a Maydl gastric fistula combined with gastrojejunostomy. The latter is occluded during periods of study. In this preparation the responses to sham feeding and to insulin-induced hypoglycemia were reduced approximately 10-fold, reiterating the significant synergistic effect of gastrin on vagal stimulation of the parietal cell mass. However, significant acid secretion could still be induced in this preparation by both sham feeding and insulin-induced hypoglycemia.

Topics: Animals; Dogs; Gastric Juice; Gastrins; Hypoglycemia; Insulin; Pyloric Antrum; Stomach; Vagus Nerve

Topics: Animals; Dogs; Epinephrine; Gastrins; Hypoglycemia; Insulin; Vagotomy

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

The effect of insulin-induced hypoglycaemia on serum group I pepsinogens (PG I), serum gastrin, and plasma secretin, and on gastric H+ and pepsin secretion was studied on 2 consecutive days in six healthy male students. The hypoglycaemia elicited a significant rise in serum PG I on both days. Furthermore, an increase in basal serum PG I was noted from the first to the second day, with a further increase the third day. Serum gastrin, which was not significantly affected, nevertheless tended to peak immediately after the nadir of the blood glucose value. Plasma secretin, on the other hand, fell significantly during gastric suction before the injection of insulin on the second day and non-significantly on the first day. A further declining tendency in plasma secretin was observed after insulin injection. Gastric H+ and pepsin outputs increased significantly on both days. There was no significant difference in gastric H+ response on the 2 days, whereas peak gastric pepsin output was significantly reduced on the second day. It is concluded that the rise in serum PG I probably reflects an increased synthesis of pepsinogens and that the fall in peak gastric pepsin output on the second day may reflect reduced storage of pepsinogens in the chief cells.

Topics: Blood Glucose; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Hypoglycemia; Injections, Intravenous; Insulin; Male; Pepsin A; Pepsinogens; Secretin; Time Factors

We have previously demonstrated that insulin hypoglycemia releases antral gastrin by a pH sensitive mechanism in duodenal ulcer (DU) patients. The effect of vagotomy per se on the hypoglycemic release of gastrin therefore might be obscured by alterations in antral pH. In the present study on 11 DU patients, the gastric acid response to intravenously administered insulin (0.2 units/kg-1) was determined before and after selective vagotomy with pyloroplasty (SV + PP). In another preoperative and postoperative test on each patient, the serum gastrin test, the serum gastrin response (radioimmunoassay) to insulin was determined during gastric perfusion with citrate-phosphate buffer pH 7.0. By adjusting the perfusion rate, the intragastric pH was maintained at 5.0 or higher. SV + PP abolished the acid response to insulin in four and reduced the response by 80% to 95% in another six patients. Gastric buffer perfusion or SV + PP did not alter the basal serum gastrin level. The increase of serum gastrin level after insulin was significantly (P less than 0.01) reduced by SV + PP. Before operation the integrated serum gastrin response to insulin was significant (P less than 0.01). SV + PP reduced the response to one-third. The effect of SV + PP on the hypoglycemic release of gastrin varied among the patients but no relationship was found to the effect on the acid response, nor to the variations of the volume or pH of the perfusate (pH range, 5.0 to 7.5). It is concluded that insulin hypoglycemia releases antral gastrin by a vagal and probably also by a nonvagal mechanism and that both mechanisms are pH sensitive.

Topics: Adult; Duodenal Ulcer; Gastrins; Humans; Hypoglycemia; Insulin; Male; Middle Aged; Perfusion; Pyloric Antrum; Vagotomy

The sympathetic nervous system is of major importance for the regulation of several physiologic functions. Drugs that inhibit the actions of catecholamines and adrenergic drugs are used in the treatment of many clinical disorders. The potential role of catecholamines in a number of human diseases has, however, until recent years been studied to a limited extent only due to lack of methods for quantitation of sympathetic nervous activity. After the development of enzymatic isotope-derivative assays, reliable measurements of noradrenaline and adrenaline became available. Studies in man have shown that plasma noradrenaline is an index of sympathetic nervous activity. The present survey deals with noradrenaline and adrenaline concentrations in blood, tissue, and cerebrospinal fluid in a number of clinical disorders viz. arterial hypertension, duodenal ulcer, malignant tumors, primary depressive illness, and ketotic hypoglycemia.

Topics: Adult; Blood Pressure; Child; Clonidine; Depression; Duodenal Ulcer; Epinephrine; Female; Gastrins; Heart Rate; Humans; Hypertension; Hypoglycemia; Ketosis; Male; Middle Aged; Neoplasms; Norepinephrine; Sympathetic Nervous System

A patient initially showed symptoms of peptic ulcer disease in 1953 and was later found to have hypercalcemia and hyperparathyroidism. Peptic ulcer symptoms persisted after parathyroidectomy, and results of studies provided evidence of the Zollinger-Ellison syndrome. Evaluation of the patient's family showed a classic pattern of multiple endocrine adenomatosis type 1. The patient underwent total gastrectomy and excision of a gastrin cell adenoma in 1971 with relief of symptoms, but with persistent hypergastrinemia. He remained in good health until January 1976, when symptoms of hypoglycemia developed. Results of laboratory studies were compatible with the diagnosis of a pancreatic beta-cell adenoma. At the time of operation, an adenoma of the head of the pancreas was found. The tumor was excised; no other metastatic tumors were found. The tumor was compatible with a beta-cell adenoma and was found to contain high concentrations of insulin; there was no important amount of gastrin. Symptoms of hypoglycemia have entirely disappeared.

Topics: Adenoma; Adenoma, Islet Cell; Gastrins; Humans; Hypoglycemia; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatic Neoplasms

The significance of antral pH for the basal serum level of immunoreactive gastrin and for the release of gastrin during insulin hypoglycemia has been studied in duodenal ulcer (DU) patients. To permit paired comparisons, 14 DU patients underwent two or three tests with insulin. Venous blood samples were collected at fixed intervals for determination of gastrin (radioimmunoassay). In the first insulin test, the gastric juice was aspirated; in the second test, the stomach was perfused with citrate-phosphate buffer, pH 7.0; and in the third test the stomach was perfused with 0.1M HCl, pH 1.0. The rate of buffer or acid perfusion was adjusted, and the pH of the perfusate was kept above 5.0 and below 1.3, respectively. Gastric perfusion with buffer or acid for 1 hour did not affect the basal serum gastrin level, nor did perfusion with buffer for 3 hours. Insulin hypoglycemia stimulated acid secretion and produced a significant integrated serum gastrin response during gastric aspiration, but the gastrin response was four times greater during buffer perfusion. Acid perfusion abolished the gastrin response. From our previous and present findings, it is concluded that the gastrin in serum during basal conditions is of extra-antral origin and is independent of antral pH. Insulin hypoglycemia releases antral gastrin by a pH-sensitive mechanism in DU patients; the release is suppressed at pH 1.3 or less and also is markedly inhibited when the gastric juice is aspirated.

Topics: Adult; Buffers; Duodenal Ulcer; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Hypoglycemia; Insulin; Male; Middle Aged; Pyloric Antrum; Secretory Rate; Suction

Topics: Adenoma, Islet Cell; Gastrins; Glucagon; Humans; Hypoglycemia; Pancreatic Neoplasms; Skin Manifestations; Zollinger-Ellison Syndrome

Fasting gastrinemia in cirrhotics (48.35 +/- 2.77 pg/ml) was higher than in normal controls (32.93 +/- 0.75 pg/ml; P less than 0.001). After insulin-induced hypoglycemia, the mean increase of gastrin above basal level was 42.29 +/- 1.92 pg/ml in controls and 10.85 +/- 5.05 pg/ml in cirrhosis (P less than 0.001). BAO was 2.53 +/- 0.36 mEq/h in controls and 0.42 +/- 0.004 mEq/h in cirrhotics (P less than 0.001). After i.v. insulin, TAO was 8.42 +/- 0.72 mEq/h in controls and 3.06 +/- 0.26 mEq/h in cirrhotics (P less than 0.001). The authors suggest that the lack of an adequate gastrin and acid response to the hypoglycemic stimulus in cirrhotics might be accounted for by a decreased insulin sensitivity.

Topics: Adult; Aged; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Liver Cirrhosis; Male; Middle Aged

Traditionally it is taught that hypoglycaemia may cause a clinical picture which mimics a variety of neurological and psychiatric disorders. Yet patients with insulinoma continue to baffle many medical specialists, who presumably are not sufficiently aware of the clinical features of hypoglycaemia. After examining medical records of seventeen patients, diagnosed as suffering from "insulinoma" in major Melbourne hospitals from 1971 to 1976, it was evident that these patients frequently undergo extensive investigations for supposed neurological disorders, the correct diagnosis being missed until they develop catastrophic symptoms. Of these seventeen patients, the diagnosis was made with reasonable speed in only six cases, while eight patients were initially discharged from hospital with a completely erroneous diagnosis. It seems likely that a number of patients with insulinoma, whose symptoms are less dramatic than those reported here, are being mistakenly treated as having epileptiform or psychiatric disorders.

Topics: Adenoma, Islet Cell; Adolescent; Adult; Diagnostic Errors; Female; Gastrins; Humans; Hypoglycemia; Male; Middle Aged; Pancreatic Neoplasms; Proinsulin; Time Factors

Both vagal and sympathetic innervation been have described as influencing hormone release from the gastrointestinal tract and pancreas. The role of neural influences on the release of gastrin, glucagon, and secretin has been studied using the potent autonomic nerve stimulus of hypoglycaemia. Healthy subjects were each rendered hypoglycaemic by insulin 0.2 units/kg on three occasions: after atropine 20 microgram/kg: after propranolol 160 mg orally, and without prior drug administration. Adequate beta-blockade was confirmed by observation of the pusle rate response to a standard exercise at the end of the experiment, and by measurements of plasma propranolol levels. Hypoglycaemia failed to produce a rise in plasma gastrin under either propranolol or control conditions but a significant rise was noted with prior atropinisation. The glucagon response to hypoglycaemia, when measured with either the C- or N-terminal reactive antibodies, was found not to be influenced to any significant extent by either beta-blockade or atropinisation. No alteration in plasma secretin levels was noted during hypoglycaemia. It therefore appears that neural influences are relatively unimportant in the release of gastrin, glucagon, and secretin in man.

Topics: Adult; Atropine; Autonomic Nervous System; Female; Gastric Juice; Gastrins; Glucagon; Humans; Hypoglycemia; Male; Propranolol; Secretin; Secretory Rate

Topics: Animals; Dogs; Gastrins; Histamine; Hypoglycemia; Insulin; Norepinephrine; Serotonin

In 50 duodenal ulcer patients acid and gastrin secretory responses were determined in the fasting state and after insulin hypoglycemia. Completeness of vagotomy was assessed by multiple criteria. In all three groups of patients studied, i.e., the unoperated, the incomplete and the complete vagotomy groups, and initial gastrin inhibition was observed, the inhibition being minimal, moderate, adn exaggerated, respectively. This inhibitory phase was followed by a significant rise in gastrin the unoperated and the incomplete vagotomy groups, the rise being significantly higher in the latter. This rise was insignificant in those with complete vagotomy. The evidence suggests the presence of both an inhibitory and a releasing mechanism for gastrin release. The ratio of basal serum gastrin to postinsulin gastrin separates complete and incomplete vagotomy without overlap.

Topics: Duodenal Ulcer; Food; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Parasympathetic Nervous System; Vagotomy

There is well documented evidence indicating in-appropriately high basal gastrins in patients with duodenal ulcer disease. After stimulation by protein meals, calcium infusion, and insulin-induced hypoglycemia there appears to be an exaggerated release of gastrin in patients with duodenal ulcers compared to control subjects. Vagotomy in general tends to increase serum gastrin by decreasing acid secretion and allowing less inhibition for antral gastrin release. This increase appears less with selective vagotomy and parietal cell vagotomy compared to truncal vagotomy, suggesting vagal inhibition of gastrin release outside the antrum. Antrectomy may decrease serum gastrins by removing a major source of the hormone. However, extra antral gastrin sources, if stimulated properly, may result in little postoperative change.

Topics: Calcium; Dietary Proteins; Duodenal Ulcer; Gastrectomy; Gastrins; Humans; Hypoglycemia; Proteins; Pyloric Antrum; Pylorus; Stomach Ulcer; Vagotomy; Zollinger-Ellison Syndrome

The release of gastrin by insulin hypoglycaemia was studied in man before and after vagotomy. Completeness of vagotomy was judged by the gastric acid response to the same hypoglycaemia, using several criteria including one that allows for pyloric losses and duodenogastric reflux. A total of 137 tests was performed on 10 subjects. The plasma gastrin concentration was found to rise in the preoperative studies and also in the postoperative studies no matter what type of vagotomy had been performed or what criteria of completeness of vagotomy were used. We concluded that gastrin can be released in response to hypoglycaemia in the absence of the vagus nerve.

Topics: Adult; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Middle Aged; Time Factors; Vagotomy

Topics: Food; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Hypoglycemia; Meat; Secretory Rate

Small pieces of pancreatic tissue were obtained at surgery from a subtotal pancreatectomy performed in a 45-day-old child suffering from intractable neonatal hyperinsulinic hypoglycemia. Histological examination was performed using aldehyde fuchsin, Grimelius', and Hellerström-Hellman's stainings, and immunoperoxidase labeling of insulin and gastrin. The pancreatic tissue before explantation showed numerous and sometimes hyperplastic islets, together with isolated insulin-, glucagon-, and gastrin-containing cells scattered among the exocrine tissue, in aspects similar to "B cell nesidioblastosis." These features could be interpreted as an acinoinsular transformation and/or an embryonic malformation. Extralobular endocrine islet formation by budding from ductular structures was evoked, suggesting the persistency of embryonic properties. The pieces were cultivated on rooster plasma coagulum covered with culture medium. In vitro, endocrine cells survived for 43 days, with outgrowth from the explant and with retention of their secretory abilities. After each medium renewal, radioimmunoassays were performed on the culture medium; they showed that insulin and glucagon secretions decreased with time. On the contrary, secretion of immunoreactive gastrin progressively increased, and kept up to 43 days, with subcultures. Some explants developed in a peculiar way, outgrowing as epithelial layers rich in gastrin-secreting cells as indicated by radioimmunoassays performed after they were reexplanted.

Topics: Cell Movement; Culture Media; Culture Techniques; Epithelial Cells; Epithelium; Gastrins; Glucagon; Humans; Hypoglycemia; Infant; Insulin; Insulin Secretion; Islets of Langerhans; Pancreas; Pancreatectomy; Pancreatic Ducts

The surgical physiology of the vagus is reviewed with respect to vagotomy in the treatment of duodenal ulcer. All types of vagotomy (truncal, selective gastric, or proximal gastric) produce similar reduction in acid secretion and comparable elevation in serum gastrin. The evidence is mounting that the vagus may have opposing influences on gastrin release: stimulation and inhibition. Division of only the extragastric vagal branches leads to withdrawal of an inhibitory mechanism rendering the denervated stomach more sensitive to the action of gastrin. The loss of this vagally controlled inhibitory mechanism, rather than more meticulous dissection, may explain the higher incidence of more complete vagotomies in selective than in truncal vagotomy. Proximal gastric vagotomy may be the ideal elective operation yet devised for duodenal ulcer. It does, however, cause elevation in serum gastrin and more than 90 per cent of patients after this operation will have positive insulin test in two to four years. This is higher than the positivity seen with truncal vagotomy. Results of controlled trials are needed before this operation becomes fully established.

Topics: Animals; Duodenum; Gallbladder; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hypoglycemia; Liver; Neural Inhibition; Pancreatic Juice; Peptic Ulcer; Stomach; Vagotomy; Vagus Nerve

The availability of pure intestinal hormones and the development of radioimmunoassays for their measurement has expedited research into many aspects of gastrointestinal endocrinology. A complex balance evidently exists between the different intestinal hormones and also the rest of the endocrine system. Polyendocrinopathies have been described, and, so far, two diseases due to intestinal hormone excess (Zollinger-Ellison syndrome and the syndrome of watery diarrhea, hypokalemia and achlorhydria) elucidated. It seems likely that many more gastrointestinal endocrine diseases await discovery.

Topics: Cholecystokinin; Diagnosis, Differential; Diarrhea; Digestive System; Endocrine Glands; Esophagogastric Junction; Gastrins; Gastrointestinal Hormones; Humans; Hypoglycemia; Intestinal Diseases; Intestine, Large; Pancreas; Peptic Ulcer; Prostaglandins; Pylorus; Secretin; Syndrome; Zollinger-Ellison Syndrome

In 60 uncomplicated duodenal ulcers (DU), maximum acid output (MAO) and acid output following insulin hypoglycaemia (IAO) were measured, and in 30 patients also the serum gastrin responses to insulin and to standard meals, In 7 normal controls, all 4 items were measured. Thirty-six of the DU had MAO within normal limits (normosecretors) and 24 were hypersecretors. Hypoglycaemic vagal response was higher in all DU than in normals and was, in normo-secreting DU associated with an abnormally large functioning G cell mass. This mass is not increased in hypersecreting DU and the greater vagal capacity is related to a supranormal parietal cell mass. An unknown mechanism, perhaps genetic, directs the trophic effects of an increased vagal drive to the gastrin cell mass in one group of DU and to the parietal cell mass in the other.

Topics: Adult; Duodenal Ulcer; Female; Food; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Male; Middle Aged; Pentagastrin; Secretory Rate

To study the beta-adrenergic contribution to the hypoglycaemic stimulation of gastric acid and gastrin release the effect of an equal and extensive beta-adrenergic blockade with three drugs was studied. Propranolol was investigated in 12, pindolol in 22, and practolol in 11 patients. Fasting concentration of gastrin serum and spontaneous acid secretion were not reduced by the drugs. Propranolol eliminated the gastrin response to hypoglycaemia, pindolol reduced it, and practolol caused no alteration. The hypoglycaemic acid response was reduced by all three drugs, propranolol reduced the response to one-half and was the strongest inhibitor, practolol the weakest. It is concluded that beta-adrenergic receptors may be of major importance for the hypoglycaemic stimulation of the stomach, but the receptors respond differently from the receptors in the heart.

Topics: Adult; Aged; Blood Glucose; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Male; Middle Aged; Pindolol; Practolol; Propranolol; Receptors, Adrenergic

The role of the antrum on vagally mediated pancreatic secretion was studied in 8 conscious dogs prepared with chronic pancreatic and gastric fistulae. After completion of control studies 6 were subjected to antrectomy and 2 to antroneurolysis (to interrupt submucosal nerve connections); secretory studies were repeated. With the animals secreting in response to secretin(0.03 u per kg-min) or secretin with cholecystokinin (0.05 u per kg-min), the following were administered: 1) insulin 0.2 u/kg; 2) atropine 0.2 and 0.4 mg/kg; 3) insulin after atropine. Insulin hypoglycemia elicited a marked enzyme response. Both antrectomy and antroneurolysis markedly reduced (80%) the enzyme response to insulin hypoglycemia. Atropine 0.2 mg/kg abolished the insulin response and at 0.4 mg/kg inhibited (50%) the enzyme response to cholecystokinin; these effects were unaltered by antrectomy or antroneurolysis. These experiments suggest that the pancreatic enzyme response to insulin hypoglycemia is predominantly mediated through the vagal release of antral gastrin. Furthermore, antrectomy and antroneurolysis do not affect the enzyme response to cholecystokinin nor do they alter the inhibitory effects of atropine. The inhibitio- by atropine suggests that a cholinergic background exerts a permissive effect on CCK-mediated enzyme secretion.

Topics: Animals; Atropine; Chick Embryo; Dogs; Gastrins; Hypoglycemia; Insulin; Pancreas; Pyloric Antrum; Secretin; Vagus Nerve

After removal of two large pancreactic insulinomas, although the presenting spontaneous hypoglycaemia was eliminated, severe and persisting haematemesis and melaena supervened with a rise in serum gastrin. The patient had multiple endocrine adenopathy (pituitary, parathyroids and islet cells), but no evidence of a pancreatic gastrin-producing tumour. After emergency gastric operation for the bleeding, the serum gastrin remained high until the hypercalcaemia and hyperparathyroidism had been corrected by subtotal parathyroidectomy. Immunofluorescence studies showed gastrin in the parathyroid tissue.

Topics: Adenoma, Islet Cell; Endocrine System Diseases; Fluorescent Antibody Technique; Gastrins; Glucose Tolerance Test; Hormones, Ectopic; Humans; Hyperparathyroidism; Hypoglycemia; Male; Middle Aged; Pancreatic Neoplasms; Parathyroid Glands

L-asparaginase (140,000 units) infused into the hepatic artery resulted in a remission from disabling hypoglycaemia for nine months in a man with islet cell carcinoma of the pancreas and hepatic metastases. The tumour produced insulin and gastrin with resulting hypoglycaemia and recurrent peptic ulceration which were unresponsive to other drugs. Following L-asparaginase there was a fall in both plasma and insulin and gastrin.

Topics: Adenoma, Islet Cell; Asparaginase; Gastrins; Humans; Hypoglycemia; Insulin; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms

Serum gastrin, plasma adrenaline, and blood glucose concentration were measured in 12 patients during insulin-induced hypoglycemia. Six patients had a duodenal ulcer, and 6 patients, 2 to 3 months earlier, had undergone a selective gastric vagotomy due to a duodenal ulcer. The lowest blood glucose concentration was obtained 30 min after the injection of insulin. The rise in plasma adrenaline showed a significant correlation with the degree of hypoglycemia attained. Serum gastrin was approximately doubled in both groups of subjects during the test. There was a strong correlation between rise in serum gastrin expressed in percentage of the basal value and the plasma adrenaline during hypoglycemia. In other experiments, adrenaline was infused intravenously in normal subjects in amounts (6 mug per min for 20 min) resulting in plasma concentrations comparable to those seen during the infusion. It is concluded that adrenaline is a hitherto little recognized factor influencing the gastrin response to hypoglycemia.

Topics: Adult; Blood Glucose; Duodenal Ulcer; Epinephrine; Gastric Acidity Determination; Gastrins; Humans; Hypoglycemia; Infusions, Parenteral; Insulin; Male; Middle Aged; Radioimmunoassay; Secretory Rate; Stomach; Vagotomy

Serum gastrin concentrations were measured in 75 subjects of blood group O and in 75 subjects of other blood groups. Gastrinaemia both basally and following stimulation by glycine drink or by insulin hypoglycaemia did not show any statistically significant differenc in blood group O people as compared to subjects of other blood groups. It is concluded that the claimed relationship between blood group O and parietal cell hyperplasia cannot be considered as secondary to a relationship between blood group O and increased gastrin-producting G cell mass.

Topics: ABO Blood-Group System; Adult; Female; Gastrins; Glycine; Humans; Hypoglycemia; Insulin; Male; Middle Aged

Topics: Blood Glucose; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Vagus Nerve

Topics: Animals; Bicarbonates; Cold Temperature; Dogs; Gastric Fistula; Gastrins; Hydrochloric Acid; Hypoglycemia; Injections, Intravenous; Insulin; Pyloric Antrum; Stimulation, Chemical; Vagus Nerve

Topics: Adult; Atropine; Blood Glucose; Depression, Chemical; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Iodine Radioisotopes; Male; Radioimmunoassay; Secretory Rate; Stimulation, Chemical; Sulfates; Time Factors

Topics: Duodenal Ulcer; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Iodine Radioisotopes; Male; Middle Aged; Radioimmunoassay; Vagotomy; Vagus Nerve

Topics: Gastrins; Humans; Hypoglycemia; Insulin; Radioimmunoassay; Vagotomy

Topics: Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Pyloric Antrum; Radioimmunoassay; Vagotomy; Vagus Nerve

Topics: Anemia, Pernicious; Animals; Antibody Specificity; Cross Reactions; Dietary Proteins; Duodenal Ulcer; Gastrins; Humans; Hypoglycemia; Immune Sera; Insulin; Iodine Radioisotopes; Rabbits; Radioimmunoassay; Stomach Ulcer; Swine; Vagotomy; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Binding, Competitive; Blood Glucose; Female; Gastric Acidity Determination; Gastric Mucosa; Gastrins; Glucagon; Glucose Tolerance Test; Growth Hormone; Humans; Hypoglycemia; Insulin; Intestine, Small; Liver; Male; Middle Aged; Pancreas; Postgastrectomy Syndromes; Radioimmunoassay; Receptors, Drug

Topics: Adenoma; Adult; Aged; Blood Glucose; Diazoxide; Duodenal Ulcer; Female; Gastrectomy; Gastrins; Glucagon; Hormones, Ectopic; Humans; Hyperparathyroidism; Hypoglycemia; Insulin; Insulin Secretion; Lymphatic Metastasis; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreatectomy; Pancreatic Neoplasms; Parathyroid Neoplasms; Peptic Ulcer Perforation; Splenectomy; Zollinger-Ellison Syndrome

Topics: Blood Glucose; Gastric Juice; Gastrins; Humans; Hypoglycemia; Injections, Intravenous; Insulin; Stomach; Vagotomy

Topics: Adult; Blood Glucose; Drainage; Duodenal Ulcer; Female; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Male; Pentagastrin; Radioimmunoassay; Secretory Rate; Stimulation, Chemical; Time Factors

Topics: Adult; Blood Glucose; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Male; Methods; Middle Aged; Vagotomy

Topics: Adult; Autopsy; Bone Neoplasms; Calcinosis; Gastrins; Humans; Hypoglycemia; Liver; Liver Neoplasms; Male; Neoplasm Metastasis; Pancreatic Neoplasms; Radiography; Stomach; Zollinger-Ellison Syndrome

Topics: Adult; Aged; Gastric Juice; Gastrins; Humans; Hypoglycemia; Inhalation; Insulin; Male; Middle Aged; Radioimmunoassay

Topics: Adult; Aged; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Intubation, Gastrointestinal; Male; Middle Aged; Radioimmunoassay

Topics: Acetylcholine; Analysis of Variance; Animals; Blood Glucose; Dogs; Duodenum; Eating; Gastric Fistula; Gastric Juice; Gastrins; Hypoglycemia; Immunoassay; Insulin; Muscle Denervation; Pepsin A; Pyloric Antrum; Stimulation, Chemical; Vagus Nerve

Topics: Blood Glucose; Duodenal Ulcer; Gastrectomy; Gastrins; Glucose; Humans; Hypoglycemia; Insulin; Pyloric Antrum; Radioimmunoassay; Time Factors

Topics: Animals; Dogs; Gastric Fistula; Gastric Juice; Gastrins; Hypoglycemia; Insulin; Meat; Stomach; Vagus Nerve

Topics: Animals; Dogs; Gastric Fistula; Gastric Juice; Gastrins; Hypoglycemia; Insulin; Meat; Stomach; Vagotomy

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

A radioimmunoassay for gastrin was set up and its sensitivity and specificity were studied. The assay was then used to investigate the plasma gastrin responses in man to a normal meal and to stimulation by insulin hypoglycaemia or by instilling meat extract into the stomach. The results showed that insulin and meat extract produced very similar plasma gastrin responses which were certainly not less than those produced by feeding. However, the acid secretory response to insulin was greater than that to meat extract. This indicated that the tests acted in different ways and both may be useful in the assessment of gastric secretion.

Topics: Animals; Duodenal Ulcer; Food; Gastric Juice; Gastric Mucosa; Gastrins; Humans; Hypoglycemia; Insulin; Iodine Isotopes; Meat; Rabbits; Radioimmunoassay

Topics: Adrenal Gland Diseases; Endocrine System Diseases; Erythrocytes; Female; Gastrins; Gynecomastia; Hormones, Ectopic; Humans; Hypercalcemia; Hyperplasia; Hyperthyroidism; Hypoglycemia; Male; Malignant Carcinoid Syndrome; Metabolic Diseases; Neoplasms; Neurologic Manifestations; Polycythemia; Prognosis; Puberty, Precocious; Vasopressins

Topics: Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Radioimmunoassay

Topics: Duodenal Ulcer; Female; Gastrins; Humans; Hypoglycemia; Injections, Intravenous; Insulin; Male; Radioimmunoassay; Stomach Ulcer; Time Factors; Vagotomy; Vagus Nerve

Topics: Adult; Autoanalysis; Blood Glucose; Duodenal Ulcer; Female; Gastric Acidity Determination; Gastrins; Humans; Hypoglycemia; Insulin; Male; Middle Aged; Radioimmunoassay; Vagotomy; Vagus Nerve

Topics: Bicarbonates; Esophagogastric Junction; Esophagus; Gastrectomy; Gastric Juice; Gastrins; Humans; Hydrogen-Ion Concentration; Hypoglycemia; Insulin; Muscle, Smooth; Pressure; Sodium; Stimulation, Chemical; Vagotomy; Vagus Nerve

Serum gastrin has been measured by radioimmunoassay in normal subjects and patients with proven duodenal ulcer in response to insulin hypoglycaemia in conjunction with manoeuvres to decrease the intragastric acidity. Insulin hypoglycaemia alone caused a rise in the serum gastrin level from 5 +/- 1.0 to 49 +/- 2.9 pg/ml in duodenal ulcer and from 17 +/- 5.6 to 42 +/- 7.7 pg/ml in normals. With complete intragastric neutralization of acid and the same stimulus, the rise in duodenal ulcer was from 5 +/- 1.3 to 128 +/- 13.6 pg/ml and in normals from 13 +/- 2.6 to 84 +/- 2.6 pg/ml. These studies suggest an increased production rate of gastrin in response to vagal stimulation in duodenal ulcer, and indicate the precise role of acid inhibition in the control of gastrin release and support the concept of both an increased ;G cell' mass and parietal cell mass in duodenal ulcer. They have also offered an explanation of the variable vagal stimulation of gastrin release in normal subjects.

Topics: Bicarbonates; Blood Glucose; Duodenal Ulcer; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Radioimmunoassay; Vagus Nerve

Topics: Adult; Calcium; Gastrectomy; Gastric Mucosa; Gastrins; Humans; Hypoglycemia; Insulin; Male; Middle Aged; Neoplasm Metastasis; Vagotomy; Zollinger-Ellison Syndrome

Topics: Adenoma; Adenoma, Islet Cell; Gastrins; Humans; Hyperinsulinism; Hypoglycemia; Insulin; Microscopy, Electron; Multiple Endocrine Neoplasia; Neoplasm Metastasis; Pancreas; Zollinger-Ellison Syndrome

Topics: Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Male; Vagus Nerve

Topics: Gastric Acidity Determination; Gastric Juice; Gastrins; Humans; Hypoglycemia; Insulin; Peptides

Topics: Adenoma, Islet Cell; Antibiotics, Antineoplastic; Blood Glucose; Female; Gastrins; Glucagon; Hormones, Ectopic; Humans; Hypoglycemia; Insulin; Insulin Secretion; Liver Neoplasms; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Radionuclide Imaging

Topics: Animals; Dogs; Gastric Acid; Gastric Mucosa; Gastrins; Hypoglycemia; Insulin; Pyloric Antrum; Vagotomy; Vagus Nerve

Topics: Animals; Biological Transport; Carbon Isotopes; Chlorides; Dogs; Gastrectomy; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Hydrogen-Ion Concentration; Hypoglycemia; Insulin; Peptides; Sodium; Vagus Nerve

Topics: Animals; Depression, Chemical; Dogs; Gastric Juice; Gastric Mucosa; Gastrins; Gastrostomy; Hexoses; Histamine; Hypoglycemia; Insulin; Neostigmine; Peptides; Stimulation, Chemical; Stomach; Vagotomy; Vagus Nerve

Topics: Animals; Bethanechol Compounds; Dogs; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Gastrins; Histamine; Hypoglycemia; Parasympathomimetics; Pepsin A; Pharmacology; Physiology; Stomach; Vagotomy

Topics: Animals; Blood Glucose; Dogs; Gastric Juice; Gastrins; Histamine; Hypoglycemia; Hypoglycemic Agents; Insulin; Research; Vagus Nerve

Topics: Dogs; Gastric Juice; Gastrins; Hypoglycemia; Injections; Injections, Intravenous; Insulin; Pharmacology; Research