Distinct effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 on insulin secretion and gut motility.
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Distinct effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 on insulin secretion and gut motility. / Miki, Takashi; Minami, Kohtaro; Shinozaki, Hidehiro; Matsumura, Kimio; Saraya, Atsunori; Ikeda, Hiroki; Yamada, Yuichiro; Holst, Jens Juul; Seino, Susumu.
In: Diabetes, Vol. 54, No. 4, 2005, p. 1056-63.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 54
SP - 1056
EP - 1063
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 4
ER -
ID: 8418067