beta-Hydroxybutyrate increases the insulin sensitivity of adipocyte glucose transport at a postreceptor level.
The effect of insulin on glucose transport (2-deoxyglucose uptake) in adipocytes was measured in the absence and in the presence of 10 mM sodium-DL-beta-hydroxybutyrate. The ketone body had little or no effect on the basal or the maximally insulin-stimulated rate of transport. However, beta-hydroxybutyrate potentiated the effect of submaximal concentrations of insulin, i.e., it resulted in a leftward shift in the dose-response curve. The half-maximally effective concentration of insulin was decreased by approximately 30% from 0.58 ng/ml to 0.40 ng/ml. beta-Hydroxybutyrate caused a slight (approximately 10%) increase in 125I-insulin binding to the cells. To determine whether this small increase in insulin binding is responsible for the increased insulin sensitivity in the presence of the ketone, two mimickers of insulin action were used: a serum containing anti-insulin receptor antibodies and hydrogen peroxide. beta-Hydroxybutyrate increased the sensitivity of glucose transport to stimulation by the anti-receptor antibody, demonstrating that insulin itself does not have to be present. beta-Hydroxybutyrate also potentiated the effect of hydrogen peroxide (which acts at a level distal to the insulin receptor) even in cells that had been depleted of insulin receptors by trypsin treatment. Therefore, beta-hydroxybutyrate acts, at least partly, at a post-insulin receptor level. Adenosine increases the insulin sensitivity of adipocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
D020155:3-Hydroxybutyric Acid; D000241:Adenosine / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000494:pharmacology; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006885:Hydroxybutyrates / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*
D006885:Hydroxybutyrates; D007328:Insulin; D003847:Deoxyglucose; D006861:Hydrogen Peroxide; D011972:Receptor, Insulin; D000243:Adenosine Deaminase; D005947:Glucose; D000241:Adenosine; D020155:3-Hydroxybutyric Acid