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胃抑制多肽受体和胰高血糖素样肽-1 受体敲除小鼠的胰高血糖素和胰岛素分泌、胰岛素清除率以及空腹血糖。

Glucagon and insulin secretion, insulin clearance, and fasting glucose in GIP receptor and GLP-1 receptor knockout mice.

机构信息

Metabolic Unit, National Research Council Institute of Neuroscience, Padua, Italy.

Department of Endocrinology, Diabetes and Geriatric Medicine, Graduate School of Medicine, Akita University, Akita, Japan.

出版信息

Am J Physiol Regul Integr Comp Physiol. 2019 Jan 1;316(1):R27-R37. doi: 10.1152/ajpregu.00288.2018. Epub 2018 Nov 21.

Abstract

It is not known whether GIP receptor and GLP-1 receptor knockout (KO) mice have perturbations in glucagon secretion or insulin clearance, and studies on impact on fasting glycemia have previously been inconsistent in these mice. We therefore studied glucagon secretion after oral whey protein (60 mg) and intravenous arginine (6.25 mg), insulin clearance after intravenous glucose (0.35 g/kg) and fasting glucose, insulin, and glucagon levels after standardized 5-h fasting in female GIP receptor and GLP-1 receptor KO mice and their wild-type (WT) littermates. Compared with WT controls, GIP receptor KO mice had normal glucagon responses to oral protein and intravenous arginine, except for an enhanced 1-min response to arginine, whereas glucagon levels after oral protein and intravenous arginine were enhanced in GLP-1 receptor KO mice. Furthermore, the intravenous glucose test revealed normal insulin clearance in both GIP receptor and GLP-1 receptor KO mice, whereas β-cell glucose sensitivity was enhanced in GIP receptor KO mice and reduced in GLP-1 receptor KO mice. Finally, GIP receptor KO mice had reduced fasting glucose (6.7 ± 0.1, n = 56, vs. 7.4 ± 0.1 mmol/l, n = 59, P = 0.001), whereas GLP-1 receptor KO mice had increased fasting glucose (9.1 ± 0.2, n = 44, vs. 7.7 ± 0.1 mmol/l, n = 41, P < 0.001). We therefore suggest that GIP has a limited role for glucagon secretion in mice, whereas GLP-1 is of importance for glucagon regulation, that GIP and GLP-1 are of importance for the regulation of β-cell function beyond their role as incretin hormones, and that they are both of importance for fasting glucose.

摘要

尚不清楚 GIP 受体和 GLP-1 受体敲除 (KO) 小鼠的胰高血糖素分泌或胰岛素清除是否受到干扰,此前这些小鼠的空腹血糖影响研究结果一直不一致。因此,我们研究了雌性 GIP 受体和 GLP-1 受体 KO 小鼠及其野生型 (WT) 同窝仔鼠口服乳清蛋白 (60mg) 和静脉内精氨酸 (6.25mg) 后的胰高血糖素分泌、静脉内葡萄糖 (0.35g/kg) 后胰岛素清除以及标准化 5 小时禁食后的空腹血糖、胰岛素和胰高血糖素水平。与 WT 对照组相比,GIP 受体 KO 小鼠的口服蛋白和静脉内精氨酸的胰高血糖素反应正常,除了精氨酸 1 分钟反应增强外,而 GLP-1 受体 KO 小鼠的口服蛋白和静脉内精氨酸后的胰高血糖素水平升高。此外,静脉葡萄糖试验显示 GIP 受体和 GLP-1 受体 KO 小鼠的胰岛素清除正常,而 GIP 受体 KO 小鼠的 β 细胞葡萄糖敏感性增强,GLP-1 受体 KO 小鼠的降低。最后,GIP 受体 KO 小鼠的空腹血糖降低 (6.7±0.1,n=56,vs.7.4±0.1mmol/l,n=59,P=0.001),而 GLP-1 受体 KO 小鼠的空腹血糖升高 (9.1±0.2,n=44,vs.7.7±0.1mmol/l,n=41,P<0.001)。因此,我们认为 GIP 在小鼠中对胰高血糖素分泌的作用有限,而 GLP-1 对胰高血糖素调节很重要,GIP 和 GLP-1 除了作为肠促胰岛素激素的作用外,对 β 细胞功能的调节也很重要,它们对空腹血糖都很重要。

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