Regulation of GLUT-4 phosphorylation by intracellular calcium in adipocytes.
Sustained elevations in cytosolic calcium concentrations ([Ca2+]i) have been shown to render insulin target cells resistant to insulin action. In this study we examined the mechanisms of the detrimental effect of high levels of [Ca2+]i on insulin-induced 2-deoxyglucose (2-DOG) uptake. To elevate [Ca2+]i, we incubated rat adipocytes with either 40 mM potassium (K+) or 20 ng/ml PTH for 1 h for in vitro experiments and injected rats with PTH (injections of 50 micrograms, ip, every hour for 3 h) for in vivo studies. Adipocytes with elevated [Ca2+]i demonstrated a 30% decrease in insulin-stimulated 2-DOG uptake. A calcium channel blocker (nitrendipine) and a cAMP antagonist (RpcAMP) each partially restored insulin-stimulated glucose transport, but together they completely restored 2-DOG uptake. Concomitantly, we found a significant increase in phosphorylation of GLUT-4 in adipocytes with elevated [Ca2+]i. This change in GLUT-4 phosphorylation was also attenuated by nitrendipine and RpcAMP. These observations confirm that elevated [Ca2+]i diminishes insulin-stimulated glucose transport and suggest that increased phosphorylation of GLUT-4 in adipocytes with high [Ca2+]i may alter its intrinsic activity.
Reusch
J E
JE
Medical Research Service, Veterans Affairs Medical Center, Denver, Colorado 80220.
Begum
N
N
Sussman
K E
KE
Draznin
B
B
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000037:antagonists & inhibitors; D003847:Deoxyglucose / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000494:pharmacology; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D009004:Monosaccharide Transport Proteins; D010281:Parathyroid Hormone; D009568:Nitrendipine; D003847:Deoxyglucose; D000242:Cyclic AMP; D011188:Potassium; D002118:Calcium