Differential effects of subcutaneous GLP-1 on gastric emptying, antroduodenal motility, and pancreatic function in men. 1997

J Schirra, and P Kuwert, and U Wank, and P Leicht, and R Arnold, and B Göke, and M Katschinski
Clinical Research Unit of Gastrointestinal Endocrinology, Philipps-University, Marburg, Germany.

In this study of eight healthy male volunteers, we investigated the effects of graded doses of subcutaneous glucagon like peptide-1(7-36)amide (GLP-1) on: 1) the gastric emptying pattern of a mixed liquid meal (300 kcal); 2) pancreatic enzyme secretion; 3) antroduodenal motility; and 4) the glycemic response as well as releases of insulin, C-peptide, and glucagon. GLP-1, 0.125 nmol/kg, or 0.25 nmol/kg, or placebo was injected subcutaneously 5 min before meal ingestion. Subcutaneous GLP-1 dose-dependently prolonged the lag period (i.e., the time to reach maximal velocity of gastric emptying) by 46.2% (low dose) and 93.7% (high dose) (p < .05) but left unaltered maximal emptying velocity, total emptying time, and exponential emptying rate. With and without GLP-1, a fed motor pattern was induced by the meal and was terminated by an antral phase III when 98% of the meal had emptied. In parallel to the prolonged lag period, GLP-1 dose-dependently inhibited antral and duodenal motility and coordinated antroduodenal contractions by > 50% (low dose) and > 70% (high dose) (p < .05). GLP-1 initially reduced and thereafter transiently stimulated pancreatic enzyme secretion. This pattern correlated with the prolonged lag period and mirrored the delayed gastric emptying. GLP-1 retarded and diminished the postprandial glucose peak and reduced the total plasma glucose response by 46.6% (low dose) and by 59.4% (high dose) (p < .05). Both doses of GLP-1 delayed the postprandial insulin peak, enhanced total insulin release, and diminished postprandial responses of glucagon and pancreatic polypeptide. The duration of the lag period strongly correlated with the timing of postprandial glucose and insulin peaks (p < .001). The initial delay of gastric emptying, the enhancement of postprandial insulin release, and the inhibition of postprandial glucagon release were independent determinants (p < .01-.05) of the postprandial glucose response after subcutaneous administration of GLP-1.

UI MeSH Term Description Entries
D008297 Male Males
D010179 Pancreas A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
D010187 Pancreatic Hormones Peptide hormones secreted into the blood by cells in the ISLETS OF LANGERHANS of the pancreas. The alpha cells secrete glucagon; the beta cells secrete insulin; the delta cells secrete somatostatin; and the PP cells secrete pancreatic polypeptide. Hormones, Pancreatic
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D001786 Blood Glucose Glucose in blood. Blood Sugar,Glucose, Blood,Sugar, Blood
D005746 Gastric Emptying The evacuation of food from the stomach into the duodenum. Emptying, Gastric,Emptyings, Gastric,Gastric Emptyings
D005768 Gastrointestinal Hormones HORMONES secreted by the gastrointestinal mucosa that affect the timing or the quality of secretion of digestive enzymes, and regulate the motor activity of the digestive system organs. Enteric Hormone,Enteric Hormones,Gastrointestinal Hormone,Intestinal Hormone,Intestinal Hormones,Hormone, Enteric,Hormone, Gastrointestinal,Hormone, Intestinal,Hormones, Enteric,Hormones, Gastrointestinal,Hormones, Intestinal
D005769 Gastrointestinal Motility The motor activity of the GASTROINTESTINAL TRACT. Intestinal Motility,Gastrointestinal Motilities,Intestinal Motilities,Motilities, Gastrointestinal,Motilities, Intestinal,Motility, Gastrointestinal,Motility, Intestinal
D006728 Hormones Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various ENDOCRINE GLANDS and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects. Hormone,Hormone Receptor Agonists,Agonists, Hormone Receptor,Receptor Agonists, Hormone
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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