Glucose intolerance caused by a defect in the entero-insular axis: A study in gastric inhibitory polypeptide receptor knockout mice
Glucose intolerance caused by a defect in the entero-insular axis: A study in gastric inhibitory polypeptide receptor knockout mice
复制标题
DOI：
10.1073/pnas.96.26.14843
复制
发表时间：
1999-12-21
影响因子：
11.1
通讯作者：
Seino, Y
中科院分区：
文献类型：
--
作者：
Miyawaki, K;Yamada, Y;Seino, Y
产生具有胃抑制多肽（GIP）受体基因（GIPR）的靶向突变的小鼠以确定GIP作为从肠道到胰腺β细胞的信号的介体的作用。GIPR-/-小鼠具有较高的血糖水平，在口服葡萄糖负荷后具有受损的初始胰岛素应答。虽然在GIPR+/+小鼠中，由于代偿性较高的胰岛素分泌，进食高脂饮食后的血糖水平没有增加，但由于缺乏这种增强，GIPR-/-小鼠中的血糖水平显著增加。因此，由CIP介导的早期胰岛素分泌决定了体内口服葡萄糖负荷后的葡萄糖耐量，并且由于GIP在由高胰岛素需求产生的胰岛素分泌的代偿性增强中起重要作用，因此该肠-岛轴的缺陷可能有助于糖尿病的发病机制。
Mice with a targeted mutation of the gastric inhibitory polypeptide (GIP) receptor gene (GIPR) were generated to determine the role of GIP as a mediator of signals from the gut to pancreatic beta cells, GIPR-/- mice have higher blood glucose levels with impaired initial insulin response after oral glucose load. Although blood glucose levels after meal ingestion are not increased by high-fat diet in GIPR+/+ mice because of compensatory higher insulin secretion, they are significantly increased in GIPR-/- mice because of the lack of such enhancement. Accordingly, early insulin secretion mediated by CIP determines glucose tolerance after oral glucose load in vivo, and because GIP plays an important role in the compensatory enhancement of insulin secretion produced by a high insulin demand, a defect in this entero-insular axis may contribute to the pathogenesis of diabetes.