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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Andrea Tura
  • Giovanni Pacini
  • Yuchiro Yamada
  • Yutaka Seino
  • Bo Ahrén
Organisations
External organisations
  • Aichi Cancer Center Research Institute
  • Kansai Electric Power Hospital
  • CNR Institute of Neuroscience, Pisa
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
  • Physiology

Keywords

  • GIP, GLP-1, glucagon secretion, incretin hormones, insulin clearance, mathematical modeling
Original languageEnglish
Pages (from-to)R27-R37
JournalAmerican journal of physiology. Regulatory, integrative and comparative physiology
Volume316
Issue number1
Publication statusPublished - 2019
Publication categoryResearch
Peer-reviewedYes