Regulation of hepatic pyruvate dehydrogenase kinase by insulin and dietary manipulation in vivo. Studies with the euglycaemic-hyperinsulinaemic clamp.
The provision of a high-fat diet (47% of energy as fat) for 28 days led to a significant increase in hepatic pyruvate dehydrogenase kinase activity, together with significant suppression of hepatic pyruvate dehydrogenase (active form). An enhanced hepatic pyruvate dehydrogenase kinase activity continued to be observed at 6 h after the withdrawal of the high-fat diet. Significant suppression of hepatic pyruvate dehydrogenase kinase activity was observed in post-absorptive, high-fat-fed rats after a 2.5 h euglycaemic-hyperinsulinaemic clamp, such that differences in pyruvate dehydrogenase kinase activities between control and high-fat-fed rats were no longer evident. Starvation for 24 h in rats previously maintained on standard diet also evoked a substantial increase in hepatic pyruvate dehydrogenase kinase activity. This latter response was only partially reversed by 2.5 h of euglycaemic hyperinsulinaemia. Suppression of pyruvate dehydrogenase kinase activity by 2.5 h euglycaemic hyperinsulinaemia in high-fat-fed rats was associated with a substantial increase in hepatic pyruvate dehydrogenase activity (active form) whereas no significant increase in hepatic pyruvate dehydrogenase activity (active form) was observed after 2.5 h euglycaemic hyperinsulinaemia in 24 h-starved rats. The results are consistent with the proposition that hepatic pyruvate dehydrogenase kinase responds directly to an increase in lipid oxidation which is facilitated by insulin deficiency or an impaired action of insulin.
Sugden
M C
MC
Department of Biochemistry, Faculty of Basic Medical Sciences, Queen Mary and Westfield College, University of London, UK.
Fryer
L G
LG
Holness
M J
MJ
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors; D004032:Diet; D004041:Dietary Fats / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051381:Rats; D017208:Rats, Wistar; D013217:Starvation
D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D002334:Carnitine O-Palmitoyltransferase; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D005947:Glucose