gastrins and glucagon-like-peptide-1-(7-36)amide

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

Progress in gut hormone research has considerably increased our knowledge in gastrointestinal physiology. However, this knowledge has not yet helped the understanding of common gastrointestinal diseases. A pathophysiological role of gut hormones has been established only for rare conditions This is because the clinical significance of the gut hormones is difficult to evaluate. Morphological and biochemical methods used in classical endocrinology can rarely be applied to gastrointestinal endocrinology because of the special design of the gut hormone system. Also gut hormones and autonomous nervous system overlap in their function. A defect of one system can be compensated by the other. Since the hormone-producing cells of the gut are stimulated by food ingestion, any functional or organic change of the digestive tract will alter gut hormone response. Accordingly, most changes of gut hormone levels are secondary. In some--apparently rare--instances such secondary changes contribute to the symptomatology of a pathological condition. In other instances gut hormone abnormalities mimic common diseases, thus demonstrating the heterogenecity of these conditions. More specific and reliable methods are needed to prove or to exclude the participation of gastrointestinal peptides in the pathogenesis of gastrointestinal disease. Gut peptides are an important link between nutrient entry and metabolism. This is realized by a hormonal gut factor (incretin) which augments glucose-induced insulin release. GIP is the most thoroughly investigated but not the only incretin. In addition, GIP seems to have direct effects on lipid metabolism. This would explain why fat releases more GIP than glucose. Except in the case of the metabolic hormones insulin and glucagon the therapeutic usefulness of gastrointestinal peptides has not yet been established.

Topics: Autonomic Nervous System; Duodenal Ulcer; Endocrine Glands; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Diseases; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Insulin; Insulin Secretion; Intestinal Absorption; Peptide Fragments; Peptides

Ghrelin release in man depends on the macronutrient composition of the test meal. The mechanisms contributing to the differential regulation are largely unknown. To elucidate their potential role, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), insulin, gastrin and somatostatin were examined on isolated rat stomach ghrelin secretion, which offers the advantage of avoiding systemic interactions. Basal ghrelin secretion was in a range that did not permit to consistently evaluate inhibiting effects. Therefore, the effect of gastrointestinal hormones and insulin was analyzed during vagal prestimulation. GLP-1(7-36)amide 10(-8) and 10(-7) M decreased ghrelin secretion significantly. In contrast, GIP 10(-8) and 10(-7) M augmented not only prestimulated, but also basal ghrelin secretion (p<0.05). Insulin reduced ghrelin at 10(-10), 10(-8) and 10(-6) M (p<0.05). Both gastrin 10(-8) M and somatostatin 10(-6) M also significantly inhibited ghrelin secretion. These data demonstrate that GLP-1(7-36)amide, insulin, gastrin and somatostatin are potential candidates to contribute to the postprandially observed inhibition of ghrelin secretion with insulin being the most effective inhibitor in this isolated stomach model. GIP, on the other hand, could attenuate the postprandial decrease. Because protein-rich meals do not effectively stimulate GIP release, other as yet unknown intestinal factors must be responsible for protein-induced stimulation of ghrelin release.

Topics: Animals; Dose-Response Relationship, Drug; Gastric Inhibitory Polypeptide; Gastric Mucosa; Gastrins; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Insulin; Male; Peptide Fragments; Peptide Hormones; Protein Precursors; Radioimmunoassay; Rats; Rats, Wistar; Somatostatin; Time Factors

Glucagon-like peptide (GLP)-1 inhibits acid secretion and gastric emptying in humans, but the effect on acid secretion is lost after vagotomy. To elucidate the mechanism involved, we studied its effect on vagally stimulated gastropancreatic secretion and motility in urethan-anesthetized pigs with cut splanchnic nerves, in which insulin-induced hypoglycemia elicited a marked stimulation of gastropancreatic secretion and antral motility. In addition, we studied vagally stimulated motility and pancreatic secretion in isolated perfused preparations of the porcine antrum and pancreas. GLP-1 infusion (2 pmol. kg-1. min-1) strongly and significantly inhibited hypoglycemia-induced antral motility, gastric acid secretion, pancreatic bicarbonate and protein secretion, and pancreatic polypeptide (PP) secretion. GLP-1 (at 10(-10)-10(-8) mol/l) did not inhibit vagally induced antral motility, pancreatic exocrine secretion, or gastrin and PP secretion in isolated perfused antrum and pancreas. We conclude that the inhibitory effect of peripheral GLP-1 on upper gastrointestinal secretion and motility is exerted via interaction with centers in the brain or afferent neural pathways relaying to the vagal motor nuclei.

Topics: Animals; Bicarbonates; Blood Glucose; Gastric Acid; Gastrins; Gastrointestinal Motility; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Islets of Langerhans; Muscle Contraction; Muscle, Smooth; Neurotransmitter Agents; Pancreas; Pancreatic Juice; Pancreatic Polypeptide; Parasympathetic Nervous System; Peptide Fragments; Protein Precursors; Stomach; Swine; Vagotomy; Vagus Nerve

Previous studies on the isolated perfused stomach have shown that gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1(7-36) amide (GLP-1(7-36) amide) stimulate release of somatostatin (somatostatin-like immunoreactivity, SLI). GIP produced a paradoxical increase in gastrin secretion, whereas GLP-1(7-36) was inhibitory. In the current study, the actions of synthetic (sp) and native (np) porcine and synthetic human (sh) GIP, GLP-1(7-36), and GLP-1(7-37) on SLI and gastrin secretion were compared using a gradient perfusion of peptide. All peptides increased SLI secretion at a threshold concentration of approximately 50 pmol/L (p < 0.05). The initial rate of increase in response to spGIP (119 +/- 39 pg/min) was greater than with other forms of GIP or GLP-1. Maximal increases obtained with the two porcine peptides did not differ. Gastrin secretion was increased by concentrations of spGIP and npGIP similar to those increasing SLI secretion, but the maximal response to shGIP was lower. In contrast to GIP-induced increases, both GLP-1(7-36) and GLP-1(7-37) suppressed gastrin secretion. It is concluded that human and porcine GIP, GLP-1(7-36), and GLP-1(7-37) all stimulate SLI secretion but with different maximal effects, and GIP stimulates gastrin secretion whereas both forms of GLP-1 inhibit gastrin secretion.

Topics: Animals; Gastric Inhibitory Polypeptide; Gastric Mucosa; Gastrins; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; In Vitro Techniques; Male; Peptide Fragments; Peptides; Rats; Rats, Wistar; Swine

The effect of exendin-4, a peptide of the secretin-glucagon family with high homology of amino acid sequence with glucagon-like peptide-1 (GLP-1), on gastric hormone release was investigated in the isolated perfused rat stomach. Exendin-4 dose dependently stimulated somatostatin release up to 9-fold at a concentration of 10(-7) M whereas gastrin release was inversely inhibited by up to 63%. These effects could partially be reduced by concomitant perfusion of truncated exendin-4, exendin(9-39)amide. Similarly, stimulation of somatostatin secretion and inhibition of gastrin release induced by GLP-1(7-36)amide was partially reversed by exendin-4 (9-39)amide. These data are consistent with the assumption that exendin-4 and truncated GLP-1amide exert their effects on gastric D and G cell by interaction with the same receptor.

Topics: Animals; Exenatide; Gastric Juice; Gastrins; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; In Vitro Techniques; Male; Peptide Fragments; Peptides; Rats; Rats, Sprague-Dawley; Somatostatin; Venoms