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

TY - JOUR

T1 - Distinct effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 on insulin secretion and gut motility.

AU - Miki, Takashi

AU - Minami, Kohtaro

AU - Shinozaki, Hidehiro

AU - Matsumura, Kimio

AU - Saraya, Atsunori

AU - Ikeda, Hiroki

AU - Yamada, Yuichiro

AU - Holst, Jens Juul

AU - Seino, Susumu

N1 - Keywords: Animals; Arginine; Blood Glucose; Food; Gastric Inhibitory Polypeptide; Gastrointestinal Motility; Glucagon; Glucagon-Like Peptide 1; Insulin; Islets of Langerhans; Mice; Mice, Knockout; Pancreas; Peptide Fragments; Potassium Channels; Potassium Channels, Inwardly Rectifying; Protein Precursors; Time Factors

PY - 2005

Y1 - 2005

N2 - Glucose-induced insulin secretion from pancreatic beta-cells depends critically on ATP-sensitive K(+) channel (K(ATP) channel) activity, but it is not known whether K(ATP) channels are involved in the potentiation of insulin secretion by glucose-dependent insulinotropic polypeptide (GIP). In mice lacking K(ATP) 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 K(ATP) 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 K(ATP) channel differently.

AB - Glucose-induced insulin secretion from pancreatic beta-cells depends critically on ATP-sensitive K(+) channel (K(ATP) channel) activity, but it is not known whether K(ATP) channels are involved in the potentiation of insulin secretion by glucose-dependent insulinotropic polypeptide (GIP). In mice lacking K(ATP) 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 K(ATP) 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 K(ATP) channel differently.

M3 - Journal article

C2 - 15793244

SN - 0012-1797

VL - 54

SP - 1056

EP - 1063

JO - Diabetes

JF - Diabetes

IS - 4

ER -