gastrins and Hyperinsulinism

Topics: Adenoma; Carcinoid Tumor; Endocrine System Diseases; Gastrins; Gastrointestinal Diseases; Glucagonoma; Histocytochemistry; Humans; Hyperinsulinism; Immunochemistry; Insulinoma; Islets of Langerhans; Pancreatic Diseases; Pancreatic Neoplasms; Peptic Ulcer; Somatostatinoma; Stomach; Vipoma

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: Adenoma, Islet Cell; Diagnosis, Differential; Diarrhea; Gastrins; Germany, West; Glucagon; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Malignant Carcinoid Syndrome; Pancreatic Neoplasms; Syndrome; Zollinger-Ellison Syndrome

The islet cell tumors of the pancreas are now known to produce a variety of polypeptides in addition to insulin. These include glucagon, serotonin, corticotropin, melanocyte-stimulating hormone, gastrin and a secretinlike hormone that may be VIP or a combination of such polypeptides. The development and wide availability of the newer immunoassays for the various recognized hormones as well as candidate hormones of the gut will simplify the diagnosis of these challenging tumors, which up until this time have produced symptoms that were bizarre and often fatal to the patient.

Topics: Achlorhydria; Adenoma, Islet Cell; Angiography; Calcium; Diagnosis, Differential; Diarrhea; Gastrins; Glucagon; Hormones, Ectopic; Humans; Hyperinsulinism; Hyperparathyroidism, Secondary; Neoplasm Metastasis; Pancreatic Neoplasms; Paraneoplastic Endocrine Syndromes; Zollinger-Ellison Syndrome

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

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

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

Percutaneous transhepatic sampling of blood in the portal venous system (TPVS) was used to; (1) localize hormone secreting tumors and help in differentiating tumors from diffuse disease (nesideoblastosis and hyperplasia with adenomata) in 9 patients with fasting hypoglycemia and hyperinsulinism, and (2) study the concentration an distribution of the immunoreactive peptides: insulin (IRI), gastrin (IG), glucagon (IRG), pancreatic polypeptide (hPP), and somatostatin (SRIF-LI), in the venous drainage of the uninvolved portion of the pancreas and GI tract. Localized elevations of IRI (64-920 microunits/ml) predicted tumor localization in 6 patients with single tumors that were not demonstrable angiographically. In one patient with nesideoblastosis and another with islet cell hyperplasia with adenoma, elevated IRI concentrations at multiple locations suggested a diffuse or multicentric process. Elevations of SRIF-LI in the same region as IRI elevations in one patient and of IRG in another patient suggested that these tumor produced two hormones. Some problems in the interpretation of portal venous insulin concentrations are discussed. The locations of maximum portal venous system plasma concentrations and portal-arterial gradients (mean +/- SE pg/ml) in five patients with small single insulinomas were: IG, gastrocolic trunk (126 +/- 27, 46 +/- 22); IRG, proximal splenic vein (130 +/- 30, 47 +/- 13) and gastrocolic trunk (131 +/- 23, 60 +/- 13); hPP, portal vein (164 +/- 48, 49 +/- 22); SRIF-LI, superior mesenteric vein (186 +/- 50, 57 +/- 20) and gastrocolic trunk (178 +/- 59, 55 +/- 21). It is concluded; (1) TPVS can be used successfully to localize single insulin-secreting tumors of the pancreas and to help distinguish them from diffuse disease but problems in such differentiation do occur, (2) circulating SRIF-LI and IRG are derived from both the pancreas and the gut, IG predominantly from the proximal gut and hPP from the head of the pancreas, and (3) The data provide new information for the interpretation of portal insulin concentrations in patients with organic hyperinsulinism and of hormone concentrations for localization of peptide-producing tumors of the pancreas other than insulinomas.

Topics: Adenoma; Adenoma, Islet Cell; Adult; Female; Gastrins; Glucagon; Humans; Hyperinsulinism; Insulin; Male; Middle Aged; Pancreatic Neoplasms; Pancreatic Polypeptide; Portal Vein; Somatostatin

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

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

Insulin, proinsulin, glucagon and gastrin were determined in extracts of tumors of 27 patients with pancreatic islet cell neoplasia of pancreas, in one patient with nesidioblastosis, in extracts of uninvolved portions of the pancreas in 11 of the tumor patients and of 15 control pancreases. Mean insulin concentration in solitary adenomas and in adenomas of patients with adenomatosis was higher than in control pancreases; however, in all but 1 patient the insulin concentration in neoplastic islet tissue was lower than in islet tissue of control pancreas, assuming islet volume is 1% of pancreas. The percentage of proinsulin was elevated in 52% of tumors. Adenoma insulin content correlated with increments of plasma insulin after tolbutamide administration. Insulin and proinsulin concentrations in pancreas uninvolved by tumor were not suppressed. Fasting plasma glucagon was elevated in patients with islet cell adenomatosis and in patients with islet cell carcinoma some of whom had multiple endocrine adenomatosis. The mean concentration of glucagon in tumors was lower than in control pancreases. Elevated concentration of gastrin was found in some adenomas. The data indicate: 1) insulin-secreting islet cell tumors have decreased storage capacity for insulin, 2) elevated concentration of proinsulin in tumors may be due to decreased capacity to store insulin and in some to decreased conversion of proinsulin to insulin as well, 3) tolbutamide stimulates the exaggerated release of a relatively constant fraction of insulin stored in adenomas. 4) solitary adenomas may contain excess amounts of pancreatic hormones in addition to insulin, 5) elevated plasma glucagon in patients with organic hyperinsulinism may indicate malignancy, microadenomatosis or multiple endocrine adenoma syndrome, and 6) chronic hyperinsulinism and hypoglycemia due to adenoma do not suppress insulin and proinsulin content of uninvolved pancreas.

Topics: Adenoma; Adenoma, Islet Cell; Adolescent; Adult; Aged; Antigen-Antibody Reactions; Carcinoma; Female; Gastrins; Glucagon; Humans; Hyperinsulinism; Insulin; Male; Middle Aged; Multiple Endocrine Neoplasia; Pancreas; Pancreatic Hormones; Proinsulin; Tolbutamide

Topics: Adenoma; Adult; Aged; Cushing Syndrome; Gastric Juice; Gastrins; Glucagon; Humans; Hypercalcemia; Hyperinsulinism; Islets of Langerhans; Middle Aged; Pancreatic Neoplasms; Peptic Ulcer; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Depression, Chemical; Female; Gastrins; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Middle Aged; Pancreatic Neoplasms; Somatostatin

Topics: Adenoma; Adult; Cushing Syndrome; Female; Follow-Up Studies; Gastrectomy; Gastrins; Glucagon; Humans; Hyperinsulinism; Hyperparathyroidism; Male; Middle Aged; Pancreatic Neoplasms; Secretin; Streptozocin; Zollinger-Ellison Syndrome

Topics: Adolescent; Adult; Age Factors; Aged; Child; Diagnosis, Differential; Female; Gastric Juice; Gastrins; Histamine; Humans; Hyperinsulinism; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Hormones; Pancreatic Neoplasms; Secretory Rate; Sex Factors; Zollinger-Ellison Syndrome

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

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

Topics: Animals; Atropine; Dogs; Epinephrine; Femoral Artery; Gastrins; Hyperinsulinism; Injections, Intramuscular; Injections, Intravenous; Insulin; Insulin Secretion; Islets of Langerhans; Isotonic Solutions; Pancreas; Peptides; Propranolol; Stimulation, Chemical; Veins

Topics: Adenoma, Islet Cell; Adrenal Gland Diseases; Gastrins; Glucagon; Glucose Tolerance Test; Humans; Hypercalcemia; Hyperinsulinism; Immunoassay; Insulin; Insulin Antibodies; Insulin Secretion; Multiple Endocrine Neoplasia; Neoplasm Metastasis; Parathyroid Diseases; Tolbutamide; Zollinger-Ellison Syndrome

Topics: Adenoma, Islet Cell; Adrenal Gland Neoplasms; Adult; Aged; Biological Assay; Female; Gastrectomy; Gastric Acidity Determination; Gastrins; Humans; Hyperinsulinism; Hyperparathyroidism; Male; Middle Aged; Multiple Endocrine Neoplasia; Peptic Ulcer; Pituitary Neoplasms; Radiography; Thyroid Neoplasms; Zollinger-Ellison Syndrome

Topics: Blood Flow Velocity; Dogs; Epinephrine; Gastric Acidity Determination; Gastrins; Hemodynamics; Histamine; Histamine H1 Antagonists; Hyperinsulinism; Pharmacology; Research; Stomach; Stress, Physiological; Vagus Nerve