Glucagon receptor knockout mice display increased insulin sensitivity and impaired beta-cell function
(2006) In Diabetes 55(12). p.3463-3469- Abstract
- In previous studies, glucagon receptor knockout mice (Gcgr(-/-)) display reduced blood glucose and increased glucose tolerance, with hyperglucagonemia and increased levels of glucagon-like peptide (GLP)-1. However, the role of glucagon receptor signaling for the regulation of islet function and insulin sensitivity is unknown. We therefore explored P-cell function and insulin sensitivity in Gcgr(-/-) and wild-type mice. The steady-state glucose infusion rate during hyperinsulinemic-euglycemic clamp was elevated in Gcgr(-/-) mice, indicating enhanced insulin sensitivity. Furthermore, the acute insulin response (AIR) to intravenous glucose was higher in Gcgr(-/-) mice. The augmented AIR to glucose was blunted by the GLP-1 receptor antagonist,... (More)
- In previous studies, glucagon receptor knockout mice (Gcgr(-/-)) display reduced blood glucose and increased glucose tolerance, with hyperglucagonemia and increased levels of glucagon-like peptide (GLP)-1. However, the role of glucagon receptor signaling for the regulation of islet function and insulin sensitivity is unknown. We therefore explored P-cell function and insulin sensitivity in Gcgr(-/-) and wild-type mice. The steady-state glucose infusion rate during hyperinsulinemic-euglycemic clamp was elevated in Gcgr(-/-) mice, indicating enhanced insulin sensitivity. Furthermore, the acute insulin response (AIR) to intravenous glucose was higher in Gcgr(-/-) mice. The augmented AIR to glucose was blunted by the GLP-1 receptor antagonist, exendin-3. In contrast, AIR to intravenous administration of other secretagogues was either not affected (carbachol) or significantly reduced (arginine, cholecystokinin octapeptide) in Gcgr(-/-) mice. In islets isolated from Gcgr(-/-) mice, the insulin responses to glucose and several insulin secretagogues were all significantly blunted compared with wild-type mice. Furthermore, glucose oxidation was reduced in islets from Gcgr(-/-) mice. In conclusion, the present study shows that glucagon signaling is required for normal P-cell function and that insulin action is improved when disrupting the signal. In vivo, augmented GLP-1 levels compensate for the impaired beta-cell function in Gcgr(-/-) mice. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/685271
- author
- Sorensen, Heidi ; Sörhede Winzell, Maria LU ; Brand, Christian L. ; Fosgerau, Keld ; Gelling, Richard W. ; Nishimura, Erica and Ahrén, Bo LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetes
- volume
- 55
- issue
- 12
- pages
- 3463 - 3469
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- wos:000242446800032
- scopus:33845522289
- pmid:17130493
- ISSN
- 1939-327X
- DOI
- 10.2337/db06-0307
- language
- English
- LU publication?
- yes
- id
- 91686c85-3d91-452d-96c7-22f543ef24cc (old id 685271)
- date added to LUP
- 2016-04-01 16:45:43
- date last changed
- 2024-10-27 02:34:00
@article{91686c85-3d91-452d-96c7-22f543ef24cc, abstract = {{In previous studies, glucagon receptor knockout mice (Gcgr(-/-)) display reduced blood glucose and increased glucose tolerance, with hyperglucagonemia and increased levels of glucagon-like peptide (GLP)-1. However, the role of glucagon receptor signaling for the regulation of islet function and insulin sensitivity is unknown. We therefore explored P-cell function and insulin sensitivity in Gcgr(-/-) and wild-type mice. The steady-state glucose infusion rate during hyperinsulinemic-euglycemic clamp was elevated in Gcgr(-/-) mice, indicating enhanced insulin sensitivity. Furthermore, the acute insulin response (AIR) to intravenous glucose was higher in Gcgr(-/-) mice. The augmented AIR to glucose was blunted by the GLP-1 receptor antagonist, exendin-3. In contrast, AIR to intravenous administration of other secretagogues was either not affected (carbachol) or significantly reduced (arginine, cholecystokinin octapeptide) in Gcgr(-/-) mice. In islets isolated from Gcgr(-/-) mice, the insulin responses to glucose and several insulin secretagogues were all significantly blunted compared with wild-type mice. Furthermore, glucose oxidation was reduced in islets from Gcgr(-/-) mice. In conclusion, the present study shows that glucagon signaling is required for normal P-cell function and that insulin action is improved when disrupting the signal. In vivo, augmented GLP-1 levels compensate for the impaired beta-cell function in Gcgr(-/-) mice.}}, author = {{Sorensen, Heidi and Sörhede Winzell, Maria and Brand, Christian L. and Fosgerau, Keld and Gelling, Richard W. and Nishimura, Erica and Ahrén, Bo}}, issn = {{1939-327X}}, language = {{eng}}, number = {{12}}, pages = {{3463--3469}}, publisher = {{American Diabetes Association Inc.}}, series = {{Diabetes}}, title = {{Glucagon receptor knockout mice display increased insulin sensitivity and impaired beta-cell function}}, url = {{http://dx.doi.org/10.2337/db06-0307}}, doi = {{10.2337/db06-0307}}, volume = {{55}}, year = {{2006}}, }