Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans. 2006

Juris J Meier, and Michael A Nauck, and Andrea Pott, and Kai Heinze, and Oliver Goetze, and Kerem Bulut, and Wolfgang E Schmidt, and Baptist Gallwitz, and Jens J Holst
Department of Medicine I, St. Josef-Hospital, Ruhr-University, Bochum, Germany. jmeier@mednet.ucla.edu

OBJECTIVE The gut-derived peptide glucagon-like peptide 2 (GLP-2) has been suggested as a potential drug candidate for the treatment of various intestinal diseases. However, the acute effects of GLP-2 on gastric functions as well as on glucose and lipid homeostasis in humans are less well characterized. METHODS Fifteen healthy male volunteers were studied with the intravenous infusion of GLP-2 or placebo over 120 minutes in the fasting state, and pentagastrin-stimulated gastric acid output was assessed. Another 15 healthy male volunteers were studied with a 390 minutes infusion of GLP-2 or placebo during the ingestion of a solid test meal. Gastric emptying was determined using a 13C-sodium-octanote breath test. Plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-2, free fatty acids, free glycerol, and triglycerides were determined. RESULTS GLP-2 administration led to a marked increase in glucagon concentrations both in the fasting state and during the meal study (P < .001). Postprandial plasma concentrations of triglycerides and free fatty acids were significantly higher during GLP-2 infusion compared with placebo (P < .01), while glycerol concentrations were similar (P = .07). GLP-2 administration caused an approximately 15% reduction in pentagastrin-stimulated gastric acid and chloride secretion (P < .01), whereas gastric emptying was not affected (P = .99). CONCLUSIONS GLP-2 reduces gastric acid secretion but does not seem to have an influence on gastric emptying. The stimulation of glucagon secretion by GLP-2 may counteract the glucagonostatic effect of GLP-1. Changes in postprandial lipid excursions seem to reflect enhanced intestinal nutrient absorption during GLP-2 administration.

UI MeSH Term Description Entries
D007004 Hypoglycemic Agents Substances which lower blood glucose levels. Antidiabetic,Antidiabetic Agent,Antidiabetic Drug,Antidiabetics,Antihyperglycemic,Antihyperglycemic Agent,Hypoglycemic,Hypoglycemic Agent,Hypoglycemic Drug,Antidiabetic Agents,Antidiabetic Drugs,Antihyperglycemic Agents,Antihyperglycemics,Hypoglycemic Drugs,Hypoglycemic Effect,Hypoglycemic Effects,Hypoglycemics,Agent, Antidiabetic,Agent, Antihyperglycemic,Agent, Hypoglycemic,Agents, Antidiabetic,Agents, Antihyperglycemic,Agents, Hypoglycemic,Drug, Antidiabetic,Drug, Hypoglycemic,Drugs, Antidiabetic,Drugs, Hypoglycemic,Effect, Hypoglycemic,Effects, Hypoglycemic
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D008297 Male Males
D010919 Placebos Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol. Sham Treatment
D004763 Glucagon-Like Peptides Peptides derived from proglucagon which is also the precursor of pancreatic GLUCAGON. Despite expression of proglucagon in multiple tissues, the major production site of glucagon-like peptides (GLPs) is the INTESTINAL L CELLS. GLPs include glucagon-like peptide 1, glucagon-like peptide 2, and the various truncated forms. Enteroglucagon,Enteroglucagons,Glucagon-Like Peptide,Glucagon-Like Polypeptide,Gut Glucagon,Glucagon-Like Polypeptides,Glucagon Like Peptide,Glucagon Like Peptides,Glucagon Like Polypeptide,Glucagon Like Polypeptides,Glucagon, Gut,Peptide, Glucagon-Like,Polypeptide, Glucagon-Like
D005215 Fasting Abstaining from FOOD. Hunger Strike,Hunger Strikes,Strike, Hunger,Strikes, Hunger
D005227 Fatty Acids Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed) Aliphatic Acid,Esterified Fatty Acid,Fatty Acid,Fatty Acids, Esterified,Fatty Acids, Saturated,Saturated Fatty Acid,Aliphatic Acids,Acid, Aliphatic,Acid, Esterified Fatty,Acid, Saturated Fatty,Esterified Fatty Acids,Fatty Acid, Esterified,Fatty Acid, Saturated,Saturated Fatty Acids
D005744 Gastric Acid Hydrochloric acid present in GASTRIC JUICE. Hydrochloric Acid, Gastric,Acids, Gastric,Acids, Gastric Hydrochloric,Gastric Acids,Gastric Hydrochloric Acid,Gastric Hydrochloric Acids,Hydrochloric Acids, Gastric
D005746 Gastric Emptying The evacuation of food from the stomach into the duodenum. Emptying, Gastric,Emptyings, Gastric,Gastric Emptyings

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