Chronic glucokinase activation reduces glycaemia and improves glucose tolerance in high-fat diet fed mice.
(2011) In European Journal of Pharmacology 663. p.80-86- Abstract
- Glucokinase (GK) plays a key role in maintaining glucose homeostasis by promoting insulin secretion from pancreatic beta cells and increasing hepatic glucose uptake. Here we investigate the effects of acute and chronic GK activation on glucose tolerance and insulin secretion in mice with diet-induced insulin resistance. In the acute study, a small molecule GK activator (GKA71) was administered to mice fed a high-fat diet for 8weeks. In the long-term study, GKA71 was provided in the diet for 4weeks to high-fat diet-fed mice. Glucose tolerance was measured after intravenous glucose administration, and insulin secretion was measured both in vivo and in vitro. Acute GK activation efficiently improved glucose tolerance in association with... (More)
- Glucokinase (GK) plays a key role in maintaining glucose homeostasis by promoting insulin secretion from pancreatic beta cells and increasing hepatic glucose uptake. Here we investigate the effects of acute and chronic GK activation on glucose tolerance and insulin secretion in mice with diet-induced insulin resistance. In the acute study, a small molecule GK activator (GKA71) was administered to mice fed a high-fat diet for 8weeks. In the long-term study, GKA71 was provided in the diet for 4weeks to high-fat diet-fed mice. Glucose tolerance was measured after intravenous glucose administration, and insulin secretion was measured both in vivo and in vitro. Acute GK activation efficiently improved glucose tolerance in association with increased insulin secretion after intravenous glucose both in control and high-fat fed mice. Chronic GK activation significantly reduced basal plasma glucose and insulin, and improved glucose tolerance despite reduced insulin secretion after intravenous glucose, suggesting improved insulin sensitivity. Isolated islets from chronically GKA71-treated mice displayed augmented insulin secretion at 8.3mmol/l glucose, without affecting glucose oxidation. High-fat diet fed mice had reduced glycogen and increased triglyceride in liver compared to control mice, and these parameters were not altered by long-term GK activation. We conclude that GK activation in high-fat diet-fed mice potently reduces glycaemia and improves glucose tolerance, with combined effect both to stimulate insulin secretion from islets and improve insulin sensitivity. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1972429
- author
- Sörhede Winzell, Maria LU ; Coghlan, Matthew ; Leighton, Brendan ; Frangioudakis, Georgia ; Smith, David M ; Storlien, Leonard H and Ahrén, Bo LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- European Journal of Pharmacology
- volume
- 663
- pages
- 80 - 86
- publisher
- Elsevier
- external identifiers
-
- wos:000292431700010
- pmid:21586282
- scopus:79959308013
- pmid:21586282
- ISSN
- 1879-0712
- DOI
- 10.1016/j.ejphar.2011.05.009
- language
- English
- LU publication?
- yes
- id
- fde441c9-3df9-4922-ae85-3b402bb8087a (old id 1972429)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21586282?dopt=Abstract
- date added to LUP
- 2016-04-01 11:02:17
- date last changed
- 2024-01-07 06:54:02
@article{fde441c9-3df9-4922-ae85-3b402bb8087a,
abstract = {{Glucokinase (GK) plays a key role in maintaining glucose homeostasis by promoting insulin secretion from pancreatic beta cells and increasing hepatic glucose uptake. Here we investigate the effects of acute and chronic GK activation on glucose tolerance and insulin secretion in mice with diet-induced insulin resistance. In the acute study, a small molecule GK activator (GKA71) was administered to mice fed a high-fat diet for 8weeks. In the long-term study, GKA71 was provided in the diet for 4weeks to high-fat diet-fed mice. Glucose tolerance was measured after intravenous glucose administration, and insulin secretion was measured both in vivo and in vitro. Acute GK activation efficiently improved glucose tolerance in association with increased insulin secretion after intravenous glucose both in control and high-fat fed mice. Chronic GK activation significantly reduced basal plasma glucose and insulin, and improved glucose tolerance despite reduced insulin secretion after intravenous glucose, suggesting improved insulin sensitivity. Isolated islets from chronically GKA71-treated mice displayed augmented insulin secretion at 8.3mmol/l glucose, without affecting glucose oxidation. High-fat diet fed mice had reduced glycogen and increased triglyceride in liver compared to control mice, and these parameters were not altered by long-term GK activation. We conclude that GK activation in high-fat diet-fed mice potently reduces glycaemia and improves glucose tolerance, with combined effect both to stimulate insulin secretion from islets and improve insulin sensitivity.}},
author = {{Sörhede Winzell, Maria and Coghlan, Matthew and Leighton, Brendan and Frangioudakis, Georgia and Smith, David M and Storlien, Leonard H and Ahrén, Bo}},
issn = {{1879-0712}},
language = {{eng}},
pages = {{80--86}},
publisher = {{Elsevier}},
series = {{European Journal of Pharmacology}},
title = {{Chronic glucokinase activation reduces glycaemia and improves glucose tolerance in high-fat diet fed mice.}},
url = {{https://lup.lub.lu.se/search/files/2330662/2019043.pdf}},
doi = {{10.1016/j.ejphar.2011.05.009}},
volume = {{663}},
year = {{2011}},
}