Treatment of Type 2 diabetes mellitus based on glucagon-like peptide-1.
Glucagon-like peptide-1 (GLP-1) is a peptide hormone released from the gut mucosa in response to meal ingestion. Its actions include stimulation of all steps of insulin gene expression, as well as beta-cell growth, inhibition of glucagon secretion, inhibition of hepatic glucose production, inhibition of gastrointestinal secretion and motility, and inhibition of appetite and food intake. Physiologically, therefore, GLP-1 is thought to act as an incretin hormone (intestinal hormones that enhance meal-related insulin secretion) and as one of the hormones of the ileal brake mechanism (endocrine inhibition of gastrointestinal motility and secretion in the presence of nutrients in the lower small intestine). However, because of these same actions, the hormone can normalise the blood glucose of patients with Type 2 diabetes mellitus, and, in contradistinction to insulin and sulphonylurea, it does not cause hypoglycaemia. Therefore, treatment of Type 2 diabetes based on GLP-1 is currently being investigated. As a peptide, it must be administered parenterally, and, in addition, it is metabolised extremely rapidly. However, several methods to circumvent these problems have already been developed. A GLP-1- based therapy of diabetes mellitus and perhaps also obesity is therefore likely to become a realistic alternative to current therapies of these disorders.
Holst
J J
JJ
Department of Medical Physiology, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark. holst@mfi.ku.dk