Premium
Long‐chain fatty acyl‐coenzyme A‐induced inhibition of glucokinase in pancreatic islets from rats depleted in long‐chain polyunsaturated ω3 fatty acids
Author(s) -
Zhang Ying,
Bulur Nurdan,
Peltier Sébastien,
Carpentier Yvon A.,
Malaisse Willy J.,
Sener Abdullah
Publication year - 2008
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.1441
Subject(s) - glucokinase , polyunsaturated fatty acid , long chain , coenzyme a , pancreatic islets , chemistry , biochemistry , chain (unit) , endocrinology , islet , carnitine , medicine , biology , fatty acid , insulin , enzyme , reductase , physics , astronomy , polymer science
The metabolism of D ‐glucose was recently reported to be impaired in pancreatic islets from second generation rats depleted in long‐chain polyunsaturated ω 3 fatty acids. Considering the increased clearance of circulating non‐esterified fatty acids prevailing in these rats, a possible inhibition of glucokinase in insulin‐producing cells by endogenous long‐chain fatty acyl‐CoA was considered. The present study was mainly aimed at assessing the validity of the latter proposal. The activity of glucokinase in islet homogenates, as judged from the increase in D ‐glucose phosphorylation rate in response to a rise in the concentration of the hexose represented, in the ω 3‐depleted rats, was only 81.8 ± 4.8% ( n = 11; p < 0.005) of the paired value recorded in control animals. This coincided with the fact that the inclusion of D ‐glucose 6‐phosphate (3.0 mM) and D ‐fructose 1‐phosphate (1.0 mM) in the assay medium resulted in a lesser fractional decrease of D ‐glucose phosphorylation in ω 3‐depleted rats than in control animals. Moreover, whereas palmitoyl‐CoA (50 µM) decreased the activity of glucokinase by 38.0 ± 6.0% ( n = 4; p < 0.01) in islet homogenates from normal rats, the CoA ester failed to affect significantly the activity of glucokinase in islet homogenates from ω 3‐depleted rats. These findings afford direct support for the view that glucokinase is indeed inhibited by endogenous long‐chain fatty acyl‐CoA in islets from ω 3‐depleted rats, such an inhibition probably participating to the alteration of D ‐glucose catabolism prevailing in these islets. Copyright © 2007 John Wiley & Sons, Ltd.