Distinct effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 on insulin secretion and gut motility

T Miki, K Minami, H Shinozaki, K Matsumura… - Diabetes, 2005 - Am Diabetes Assoc
T Miki, K Minami, H Shinozaki, K Matsumura, A Saraya, H Ikeda, Y Yamada, JJ Holst
Diabetes, 2005Am Diabetes Assoc
Glucose-induced insulin secretion from pancreatic β-cells depends critically on ATP-
sensitive K+ channel (KATP channel) activity, but it is not known whether KATP channels are
involved in the potentiation of insulin secretion by glucose-dependent insulinotropic
polypeptide (GIP). In mice lacking KATP channels (Kir6. 2−/− mice), we found that
pretreatment with GIP in vivo failed to blunt the rise in blood glucose levels after oral glucose
load. In Kir6. 2−/− mice, potentiation of insulin secretion by GIP in vivo was markedly …
Glucose-induced insulin secretion from pancreatic β-cells depends critically on ATP-sensitive K+ channel (KATP channel) activity, but it is not known whether KATP channels are involved in the potentiation of insulin secretion by glucose-dependent insulinotropic polypeptide (GIP). In mice lacking KATP channels (Kir6.2−/− mice), we found that pretreatment with GIP in vivo failed to blunt the rise in blood glucose levels after oral glucose load. In Kir6.2−/− mice, potentiation of insulin secretion by GIP in vivo was markedly attenuated, indicating that KATP channels are essential in the insulinotropic effect of GIP. In contrast, pretreatment with glucagon-like peptide-1 (GLP-1) in Kir6.2−/− mice potentiated insulin secretion and blunted the rise in blood glucose levels. We also found that GLP-1 inhibited gut motility whereas GIP did not. Perfusion experiments of Kir6.2−/− mice revealed severely impaired potentiation of insulin secretion by 1 nmol/l GIP and substantial potentiation by 1 nmol/l GLP-1. Although both GIP and GLP-1 increase the intracellular cAMP concentration and potentiate insulin secretion, these results demonstrate that the GLP-1 and GIP signaling pathways involve the KATP channel differently.
Am Diabetes Assoc