Glucagon-like peptide-1 gastrointestinal regulatory role in metabolism and motility

Gastrointestinal (GI) motility, primarily gastric emptying, balances the hormonal output that takes place after food intake in order to maintain stable blood sugar. The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), work together to reduce postprandial hyperglycemia by glucose-dependent insulin secretion and inhibition of glucagon release, as well as inhibition of GI motility and gastric emptying. GLP-1 is considered the more effective of the two incretins due to its additional inhibitory effects on GI motility. It is observed that patients on treatment with GLP-1 analogues or exenatide achieve a considerable weight loss during treatment. This is of benefit to improve insulin resistance in type 2 diabetes. Furthermore, weight loss per se is of considerable benefit in an even longer health perspective. The weight loss is considered to be due to the inhibition of GI motility. This effect has been studied in animal experimentation, and from there taken to involve studies on GI motility in healthy volunteers and patients with irritable bowel syndrome (IBS). Evolving to a phase II study in IBS, the GLP-1 analogue (ROSE-010) was recently shown to be effective for treatment of acute pain attacks in IBS. Taken together, data speak in favor of GI motility as a central component not only in metabolic disorders but also in IBS, be it due to a direct relaxing effect on GI smooth muscle or a slow emptying of gastric contents resulting in a less outspoken nutritional demand on hormonal regulatory functions in the GI tract.