EFFECT OF ACIDOSIS ON INSULIN BINDING AND GLUCOSE-UPTAKE IN ISOLATED RAT ADIPOCYTES

To assess the mechanism of insulin resistance in metabolic acidosis, w e investigated insulin receptor binding and glucose uptake in isolated rat epididymal adipocytes at three pHs, acidic (pH 6.8), neutral (pH 7.4) and alkaline (pH 8.0) groups. After male Sprague-Dawley rats weig hing 220-240 g were submitted under chloral hydrate anesthesia, epidid ymal fat pads were dissected and isolated. [I-125]-insulin binding rat e was not different between alkaline and neutral groups, but that of a cidic group was markedly decreased to approximately 30% of neutral gro up at maximum specific insulin binding rate. Scatchard analysis showed that numbers of insulin receptors were not different among three grou ps, but values of binding affinity in acidic group was significantly l ower than those of the others. 2-[H-3]deoxy-D-glucose uptake of alkali ne and neutral groups were increased to reach steady state immediately , but that of acidic group increased slowly and reached at maximum whi ch was lower than the other two groups. Furthermore, 2-deoxy-D-glucose uptake against amount of bound insulin was lower in acidic group than other two groups. From these results, it is suggested that insulin re sistance in metabolic acidosis resulted from the combined defects in b inding affinity and post-binding process in the insulin receptor.