Jens F Rehfeld1, Filip K Knop2, Meena Asmar3. 1. Department of Clinical Biochemistry, University of Copenhagen, Rigshospitalet, Denmark. 2. Center for Clinical Metabolic Research, Gentofte Hospital; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen; and Steno Diabetes Center Copenhagen, Hellerup, Denmark. 3. Department of Clinical Physiology, Bispebjerg Hospital, Steno Diabetes Center, Odense University Hospital, Denmark, Copenhagen, Denmark.
Abstract
Background: Randomized and controlled trials of glucagon-like peptide-1 (GLP-1) derived drugs have shown that the most frequent adverse symptoms are gastrointestinal. Some of the side effects such as dyspepsia, nausea and upper abdominal pain may well be of gastric origin. Since the antral hormone gastrin regulates gastric secretion of acid and enzymes and contributes to the regulation of gastric motility, we examined the effect of GLP-1 on the secretion of gastrin in normal subjects and diabetes patients.Method: Plasma was sampled from ten healthy subjects and ten patients with diabetes mellitus type 1 with glucose clamped between 6 and 9 mM. GLP-1 or saline were infused for 4 h during and after a meal. Plasma concentrations of gastrin and GLP-1 were measured using specific radioimmunoassays. Results: Basal plasma concentrations of gastrin were similar in controls and patients. After the meal, the gastrin concentrations rose significantly during saline infusion, whereas the GLP-1 infusion suppressed the secretion of gastrin significantly, most pronounced in the diabetes patients.Conclusions: The results show that GLP-1 infusion suppresses the postprandial secretion of gastrin in normal subjects and even more so in the diabetes patients. The results may therefore shed further light on the upper gastrointestinal side effects of GLP-1-derived drugs in diabetic patients.
Background: Randomized and controlled trials of glucagon-like peptide-1 (GLP-1) derived drugs have shown that the most frequent adverse symptoms are gastrointestinal. Some of the side effects such as dyspepsia, nausea and upper abdominal pain may well be of gastric origin. Since the antral hormone gastrin regulates gastric secretion of acid and enzymes and contributes to the regulation of gastric motility, we examined the effect of GLP-1 on the secretion of gastrin in normal subjects and diabetespatients.Method: Plasma was sampled from ten healthy subjects and ten patients with diabetes mellitus type 1 with glucose clamped between 6 and 9 mM. GLP-1 or saline were infused for 4 h during and after a meal. Plasma concentrations of gastrin and GLP-1 were measured using specific radioimmunoassays. Results: Basal plasma concentrations of gastrin were similar in controls and patients. After the meal, the gastrin concentrations rose significantly during saline infusion, whereas the GLP-1 infusion suppressed the secretion of gastrin significantly, most pronounced in the diabetespatients.Conclusions: The results show that GLP-1 infusion suppresses the postprandial secretion of gastrin in normal subjects and even more so in the diabetespatients. The results may therefore shed further light on the upper gastrointestinal side effects of GLP-1-derived drugs in diabeticpatients.