Long-chain fatty acyl-coenzyme A-induced inhibition of glucokinase in pancreatic islets from rats depleted in long-chain polyunsaturated omega3 fatty acids.
The metabolism of D-glucose was recently reported to be impaired in pancreatic islets from second generation rats depleted in long-chain polyunsaturated omega3 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 omega3-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 omega3-depleted rats than in control animals. Moreover, whereas palmitoyl-CoA (50 microM) 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 omega3-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 omega3-depleted rats, such an inhibition probably participating to the alteration of D-glucose catabolism prevailing in these islets.
Zhang
Ying
Y
Laboratories of Experimental Hormonology and Surgery, Brussels Free University, Brussels, Belgium.
Bulur
Nurdan
N
Peltier
Sébastien
S
Carpentier
Yvon A
YA
Malaisse
Willy J
WJ
Sener
Abdullah
A
D000214:Acyl Coenzyme A / Q000493:pharmacokinetics / Q000502:physiology*; D042962:Acyl-CoA Oxidase / Q000378:metabolism*; D000818:Animals; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005260:Female; D005941:Glucokinase / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats
D000214:Acyl Coenzyme A; D015525:Fatty Acids, Omega-3; D042962:Acyl-CoA Oxidase; D005941:Glucokinase; D005947:Glucose