Stimulatory effect of lithium on glucose transport in rat adipocytes is not mediated by elevation of IP1.
Lithium has been shown to increase glucose uptake in skeletal muscle and adipose tissues. The therapeutic effect of lithium on bipolar disease is thought to be mediated by its inhibitory effect on myo-inositol-1-monophosphatase (IMPase). We tested the hypothesis that the stimulatory effect of lithium on glucose uptake results from inhibition of IMPase and the resultant accumulation of inositol monophosphates (IP1) by comparing the effects of lithium and a selective IMPase inhibitor, L-690,488, on isolated rat adipocytes. Insulin produced a concentration-dependent stimulation of 2-deoxy-D-[14C]glucose (2-DG) transport (10 microU/ml caused half-maximal activation). Acute exposure to lithium stimulated basal glucose transport activity in a concentration-dependent manner, with a threefold stimulation at 30 mM lithium. Lithium also potentiated insulin-stimulated 2-DG transport. Lithium produced a concomitant increase in IP1 accumulation. In contrast, L-690,488 increased IP1 to levels comparable to those of lithium without stimulatory effects on 2-DG transport. These results demonstrate that stimulatory effects of lithium on glucose transport are not mediated by the inhibition of IMPase and subsequent accumulation of IP1 in rat adipocytes.
Cardiovascular Disease and Diabetes Research, Monsanto Company, St. Louis, Missouri 63167, USA.
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Chen
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McMahon
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Gulve
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism*; D004164:Diphosphonates / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004822:Epididymis; D005947:Glucose / Q000378:metabolism*; D007291:Inosine Monophosphate / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011355:Prodrugs / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D004164:Diphosphonates; D004791:Enzyme Inhibitors; D007328:Insulin; D011355:Prodrugs; D007291:Inosine Monophosphate; C088378:L 690488; D007294:Inositol; D003847:Deoxyglucose; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase; D018021:Lithium Chloride; D005947:Glucose