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

First Author  Tura A Year  2019
Journal  Am J Physiol Regul Integr Comp Physiol Volume  316
Issue  1 Pages  R27-R37
PubMed ID  30462524 Mgi Jnum  J:269253
Mgi Id  MGI:6272176 Doi  10.1152/ajpregu.00288.2018
Citation  Tura A, et al. (2019) Glucagon and insulin secretion, insulin clearance, and fasting glucose in GIP receptor and GLP-1 receptor knockout mice. Am J Physiol Regul Integr Comp Physiol 316(1):R27-R37
abstractText  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 beta-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 beta-cell function beyond their role as incretin hormones, and that they are both of importance for fasting glucose.
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