Defective insulin secretion by chronic glucagon receptor activation in glucose intolerant mice.
(2016) In Journal of Endocrinology 228. p.171-178- Abstract
- Stimulation of insulin secretion by short-term glucagon receptor (GCGR) activation is well characterized, however, the effect of long-term GCGR activation on beta-cell function is not known, but of interest, since hyperglucagonemia occurs early during development of type 2 diabetes. Therefore, we examined whether chronic GCGR activation affects insulin secretion in glucose intolerant mice. To induce chronic GCGR activation, high-fat diet fed mice were continuously (2wk) infused with the stable glucagon analogue ZP-GA-1 and challenged with oral glucose and intravenous glucose +/- GLP-1. Islets were isolated to evaluate the insulin secretory response to glucose +/- GLP-1 and pancreases were collected for immunohistochemical analysis.... (More)
- Stimulation of insulin secretion by short-term glucagon receptor (GCGR) activation is well characterized, however, the effect of long-term GCGR activation on beta-cell function is not known, but of interest, since hyperglucagonemia occurs early during development of type 2 diabetes. Therefore, we examined whether chronic GCGR activation affects insulin secretion in glucose intolerant mice. To induce chronic GCGR activation, high-fat diet fed mice were continuously (2wk) infused with the stable glucagon analogue ZP-GA-1 and challenged with oral glucose and intravenous glucose +/- GLP-1. Islets were isolated to evaluate the insulin secretory response to glucose +/- GLP-1 and pancreases were collected for immunohistochemical analysis. Two-week ZP-GA-1 infusion reduced insulin secretion both after oral and intravenous glucose challenges in vivo and in isolated islets. These inhibitory effects were corrected for by GLP-1. Also, we observed increased beta-cell area and islet size. We conclude that induction of chronic ZP-GA-1 levels in glucose intolerant mice markedly reduces insulin secretion, and thus, we suggest that chronic activation of the GCGR may contribute to the failure of beta-cell function during development of type 2 diabetes. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8503825
- author
- Ahlkvist, Linda LU ; Omar, Bilal LU ; Valeur, Anders ; Fosgerau, Keld and Ahrén, Bo LU
- organization
- publishing date
- 2016
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Endocrinology
- volume
- 228
- pages
- 171 - 178
- publisher
- Society for Endocrinology
- external identifiers
-
- pmid:26698567
- scopus:84975764023
- pmid:26698567
- wos:000374956900009
- ISSN
- 1479-6805
- DOI
- 10.1530/JOE-15-0371
- language
- English
- LU publication?
- yes
- id
- 1d4d9b95-18b4-41a3-90e5-22afee2b6ee8 (old id 8503825)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26698567?dopt=Abstract
- date added to LUP
- 2016-04-04 08:36:31
- date last changed
- 2024-10-12 18:12:58
@article{1d4d9b95-18b4-41a3-90e5-22afee2b6ee8,
abstract = {{Stimulation of insulin secretion by short-term glucagon receptor (GCGR) activation is well characterized, however, the effect of long-term GCGR activation on beta-cell function is not known, but of interest, since hyperglucagonemia occurs early during development of type 2 diabetes. Therefore, we examined whether chronic GCGR activation affects insulin secretion in glucose intolerant mice. To induce chronic GCGR activation, high-fat diet fed mice were continuously (2wk) infused with the stable glucagon analogue ZP-GA-1 and challenged with oral glucose and intravenous glucose +/- GLP-1. Islets were isolated to evaluate the insulin secretory response to glucose +/- GLP-1 and pancreases were collected for immunohistochemical analysis. Two-week ZP-GA-1 infusion reduced insulin secretion both after oral and intravenous glucose challenges in vivo and in isolated islets. These inhibitory effects were corrected for by GLP-1. Also, we observed increased beta-cell area and islet size. We conclude that induction of chronic ZP-GA-1 levels in glucose intolerant mice markedly reduces insulin secretion, and thus, we suggest that chronic activation of the GCGR may contribute to the failure of beta-cell function during development of type 2 diabetes.}},
author = {{Ahlkvist, Linda and Omar, Bilal and Valeur, Anders and Fosgerau, Keld and Ahrén, Bo}},
issn = {{1479-6805}},
language = {{eng}},
pages = {{171--178}},
publisher = {{Society for Endocrinology}},
series = {{Journal of Endocrinology}},
title = {{Defective insulin secretion by chronic glucagon receptor activation in glucose intolerant mice.}},
url = {{http://dx.doi.org/10.1530/JOE-15-0371}},
doi = {{10.1530/JOE-15-0371}},
volume = {{228}},
year = {{2016}},
}