Analoga van 'glucagon-like peptide 1' (GLP-1): een oud concept als nieuwe behandeling van patiënten met diabetes mellitus type 2

- Upon ingestion of food, the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are synthesised and secreted by specialised gut cells. GLP-1 is also produced in the pancreatic islets and the central nervous system. Both incretins bind to specific G-protein-coupled receptors that are distributed throughout the body.

- Incretins potentiate meal-induced insulin production and secretion by the β-cells and lower the blood glucose level in the presence of hyperglycaemia. GLP-1 and GIP stimulate β-cell proliferation and differentiation, whereas GLP-1 only inhibits gastric emptying and glucagon secretion, reduces food intake and improves insulin sensitivity.

- Insulin-resistant and type-2 diabetic patients have an impaired incretin response to meal ingestion. However, the insulinotropic action of exogenous GLP-1, but not that of GIP, is preserved in these subjects.

- After parenteral administration, GLP-1 has an extremely short duration of action because it is rapidly degraded by the ubiquitous enzyme dipeptidyl peptidase IV (DPPIV). To prolong GLP-1 bioactivity, DPPIV-resistant GLP-1 analogues, DPPIV inhibitors and exenatide, a long-acting synthetic GLP-1 receptor agonist derived from the Gila monster hormone exendin-4, have been developed.

- Enhancement of incretin action seems a rational and promising option for the treatment of type-2 diabetes.