Pharmacological and non-pharmacological GLP-1 receptor stimulants

Abstract

Type 2 diabetes is characterised by insulin resistance and impaired insulin secretion. Both defects are detectable prior to the diagnosis of diabetes. The incretin system, comprising glucagon-like pep-tide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), has been the target of pharmacological therapies that stimulate insulin release. Macronutrients in the distal small intestine and colon result in release of GLP-1 from intestinal L-cells and GIP from intestinal K-cells. GLP-1 is rapidly degraded (within minutes) by dipeptidyl peptidase-4 (DPP-4). GLP-1 increases insulin secretion in a glucose-dependent manner. It also causes gastric deceleration and induces satiety. Most, but not all, studies demonstrate that type 2 diabetes is characterised by GLP-1 deficiency and resistance to GIP action. Exenatide and liraglutide are GLP-1 receptor agonists that are resistant to degradation by DPP-4. Both medications have been associated with improvements in insulin secretion and gly-caemic control, and significant weight loss. Recent data demonstrate that metformin and acarbose also increase GLP-1 secretion from intestinal L-cells. Amino acids, particularly glutamine, have also been shown to have GLP-1-secretagoge effects. Finally, bariatric procedures, particularly bypass and ileal interposition procedures induce GLP-1 secretion in obese subjects.