cholecystokinin and Hypoglycemia

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: 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

Thylakoids are chlorophyll-containing membranes in chloroplasts that have been isolated from green leaves. It has been previously shown that thylakoids supplemented with a high-fat meal can affect cholecystokinin (CCK), ghrelin, insulin and blood lipids in humans, and can act to suppress food intake and prevent body weight gain in rodents. This study investigates the addition of thylakoids to a high carbohydrate meal and its effects upon hunger motivation and fullness, and the levels of glucose, insulin, CCK, ghrelin and tumour necrosis factor (TNF)-alpha in overweight women. Twenty moderately overweight female subjects received test meals on three different occasions; two thylakoid enriched and one control, separated by 1 week. The test meals consisted of a high carbohydrate Swedish breakfast, with or without addition of thylakoids. Blood samples and VAS-questionnaires were evaluated over a 4-h period. Addition of thylakoids suppressed hunger motivation and increased secretion of CCK from 180 min, and prevented postprandial hypoglycaemia from 90 min following food intake. These effects indicate that thylakoids may intensify signals of satiety. This study therefore suggests that the dietary addition of thylakoids could aid efforts to reduce food intake and prevent compensational eating later in the day, which may help to reduce body weight over time.

Topics: Adult; Aged; Blood Glucose; Cholecystokinin; Diet; Dietary Carbohydrates; Dietary Supplements; Female; Ghrelin; Humans; Hunger; Hypoglycemia; Insulin; Middle Aged; Overweight; Postprandial Period; Satiation; Satiety Response; Single-Blind Method; Surveys and Questionnaires; Thylakoids; Time Factors; Tumor Necrosis Factor-alpha

Brain glucosensing neurons monitor extracellular glucose concentrations and act to defend normoglycemia. To date, the majority of these neurons have been ascribed to hypothalamic and hindbrain centers. In this issue, Garfield and colleagues (2014) demonstrate that cholecystokinin-expressing neurons in the rodent parabrachial nucleus function as glucosensors that counter-regulate hypoglycemia.

Topics: Animals; Cholecystokinin; Hypoglycemia; Hypothalamus; Male

Hypoglycemia engenders an autonomically mediated counterregulatory (CR)-response that stimulates endogenous glucose production to maintain concentrations within an appropriate physiological range. Although the involvement of the brain in preserving normoglycemia has been established, the neurocircuitry underlying centrally mediated CR-responses remains unclear. Here we demonstrate that lateral parabrachial nucleus cholecystokinin (CCK(LPBN)) neurons are a population of glucose-sensing cells (glucose inhibited) with counterregulatory capacity. Furthermore, we reveal that steroidogenic-factor 1 (SF1)-expressing neurons of the ventromedial nucleus of the hypothalamus (SF1(VMH)) are the specific target of CCK(LPBN) glucoregulatory neurons. This discrete CCK(LPBN)→SF1(VMH) neurocircuit is both necessary and sufficient for the induction of CR-responses. Together, these data identify CCK(LPBN) neurons, and specifically CCK neuropeptide, as glucoregulatory and provide significant insight into the homeostatic mechanisms controlling CR-responses to hypoglycemia.

Topics: Animals; Blood Glucose; Cholecystokinin; Hypoglycemia; Hypothalamus; Male; Mice; Parabrachial Nucleus

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

By means of radioimmunoassay procedures, cholecystokinin-(CCK) and somatostatin-(SRIF) like immunoreactivity have been studied in the dorsal hippocampal formation and in the frontoparietal cortex of the male rat in insulin-induced hypoglycaemia, leading to an isoelectric EEG pattern. It has been demonstrated that severe hypoglycaemia of 40-min-duration produces a disappearance of SRIF but not of CCK-like immunoreactivity in both cortical regions. It was found that an i.v. injection of uridine but not of saline could significantly counteract the disappearance of SRIF-like immunoreactivity induced by severe hypoglycaemia in both cortical areas. Uridine did not by itself change plasma glucose levels. It is suggested that uridine may prevent release and/or increase synthesis of cortical SRIF peptides in severe hypoglycaemia, possibly due to an action on the metabolism (e.g. by enhancing the resynthesis of phosphatidyl inositol) within the tissue of the cerebral cortex and/or on putative pyrimidine binding sites in the brain controlling SRIF synthesis and/or release. It is possible that uridine in this way may improve recovery of neuronal function within SRIF-immunoreactive neurons of the cerebral cortex after severe hypoglycaemia (which also may be true in other states of reduced metabolic support). These findings suggest a possibility to use uridine in the treatment of Alzheimer's disease and Status epilepticus.

Topics: Animals; Brain; Cerebral Cortex; Cholecystokinin; Hippocampus; Hypoglycemia; Injections, Intravenous; Insulin; Male; Partial Pressure; Peptides; Radioimmunoassay; Rats; Rats, Inbred Strains; Uridine

The control mechanisms of pyloric pressure responses have not been elucidated clearly. The purposes of this study were twofold: 1) to determine the dose-related pressure responses of the pylorus to exogenous glucagon, secretin, and cholecystokinin, and 2) to correlate changes in pyloric pressure with serum concentrations of these hormones. Pyloric pressures were measured by infusion manometry, and the serum concentrations of glucagon and secretin were quantitated using radioimmunoassays. Each of the hormones tested, glucagon, secretin, and cholecystokinin, increased the pyloric pressure significantly. The lowest active dosages tested for each of these peptide hormones were 2 micrograms.kg-1.h-1, 2 U.kg-1.h-1, and 1 U.kg-1.h-1, respectively. The maximal pyloric pressure responses recorded were 8.7 +/- 1.1 (P less than 0.05), 12.6 +/- 2.1 (P less than 0.02), and 14.8 +/- 1.7 (P less than 0.02) mmHg, respectively. The pyloric pressure responses to insulin hypoglycemia, duodenal acidification, and intraduodenal olive oil were 11.3 +/- 1.5, 13.4 +/- 1.4, and 11.3 +/- 1.4 mmHg, respectively. The serum concentrations of immunoreactive glucagon during infusion of the lowest active dosage of glucagon and insulin hypoglycemia were 801 +/- 55 and 322 +/- 12 pg/ml, respectively. The serum concentrations of immunoreactive secretin during infusion of the lowest active dosage of secretin and during duodenal acidification were 980 +/- 60 and 110 +/- 7.0 pg/ml, respectively. Although pyloric contraction can be induced by administration of exogenous glucagon, secretin, and cholecystokinin, these studies suggest that these effects may have no physiological relevance.

Topics: Cholecystokinin; Glucagon; Humans; Hypoglycemia; Insulin; Muscle Contraction; Pressure; Pylorus; Secretin

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

Topics: Adenoma; Adrenal Gland Neoplasms; Autopsy; Blood Glucose; Cholecystokinin; Diazoxide; Glucagon; Glucose; Humans; Hypoglycemia; Insulin; Islets of Langerhans; Male; Multiple Endocrine Neoplasia; Pancreatic Neoplasms; Parathyroid Neoplasms

Topics: Amino Acids; Blood Glucose; Cholecystokinin; Duodenum; Gastrointestinal Hormones; Glucose; Glucose Tolerance Test; Growth Hormone; Humans; Hypoglycemia; Infusions, Parenteral; Insulin; Insulin Secretion; Phenformin

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

Topics: Carbachol; Cholecystography; Cholecystokinin; Gallbladder; Humans; Hypoglycemia; Insulin; Vagotomy

Topics: Animals; Blood Glucose; Cholecystokinin; Dogs; Fasting; Fatty Acids, Nonesterified; Hypoglycemia; Infusions, Parenteral; Injections, Intravenous; Insulin; Portal Vein