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

Tura, Andrea; Pacini, Giovanni; Yamada, Yuchiro; Seino, Yutaka and Ahrén, Bo LU (2019) In American journal of physiology. Regulatory, integrative and comparative physiology 316(1). p.27-37
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
GIP, GLP-1, glucagon secretion, incretin hormones, insulin clearance, mathematical modeling
in
American journal of physiology. Regulatory, integrative and comparative physiology
volume
316
issue
1
pages
27 - 37
publisher
American Physiological Society
external identifiers
  • scopus:85059287585
ISSN
0363-6119
DOI
10.1152/ajpregu.00288.2018
language
English
LU publication?
yes
id
bcfde8b3-acf9-4f24-801b-742a32479edb
date added to LUP
2019-01-11 09:46:19
date last changed
2019-02-20 11:42:38
@article{bcfde8b3-acf9-4f24-801b-742a32479edb,
  abstract     = {<p>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 &lt; 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.</p>},
  author       = {Tura, Andrea and Pacini, Giovanni and Yamada, Yuchiro and Seino, Yutaka and Ahrén, Bo},
  issn         = {0363-6119},
  keyword      = {GIP, GLP-1,glucagon secretion,incretin hormones,insulin clearance,mathematical modeling},
  language     = {eng},
  number       = {1},
  pages        = {27--37},
  publisher    = {American Physiological Society},
  series       = {American journal of physiology. Regulatory, integrative and comparative physiology},
  title        = {Glucagon and insulin secretion, insulin clearance, and fasting glucose in GIP receptor and GLP-1 receptor knockout mice},
  url          = {http://dx.doi.org/10.1152/ajpregu.00288.2018},
  volume       = {316},
  year         = {2019},
}