Stimulation of cardiac glucose transport by thioctic acid and insulin.
Thioctic acid (alpha-lipoic acid) has been shown to improve insulin-regulated glucose disposal in animal models of insulin resistance and type 2 diabetic patients. In the present study, we have used isolated adult ventricular cardiomyocytes in order to analyze 1) direct effects of this compound on glucose uptake in a primary muscle cell, and 2) the interaction with the insulin signalling cascade. Both insulin and thioctic acid (2.5 mM) induced a rapid increase in 3-O-methylglucose transport to 322+/-43 and 385+/-58 (n = 5) percent of basal control, respectively. Combined stimulation did not result in an additional significant increase in the transport rate. Preincubation of cardiomyocytes with the phosphatidylinositol 3-kinase inhibitor wortmannin completely abolished the effects of insulin and thioctic acid, whereas gamma-linolenic acid selectively blocked the effect of this compound. These data show that thioctic acid mimics insulin action by activating the signalling cascade at or before the level of phosphatidylinositol 3-kinase.
Ramrath
S
S
Department of Clinical Biochemistry, German Diabetes Research Institute, Düsseldorf.
Tritschler
H J
HJ
Eckel
J
J
D019325:3-O-Methylglucose / Q000493:pharmacokinetics*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D008063:Thioctic Acid / Q000494:pharmacology*; D017965:gamma-Linolenic Acid / Q000494:pharmacology
D007004:Hypoglycemic Agents; D007328:Insulin; D019325:3-O-Methylglucose; D008063:Thioctic Acid; D017965:gamma-Linolenic Acid; D019869:Phosphatidylinositol 3-Kinases