DIABETIC STATE-INDUCED MODIFICATION OF INSULIN-STIMULATED, GLUCOSE-UPTAKE INTO AND KINASE-ACTIVITY IN, THE DIAPHRAGM MUSCLE OF GENETICALLY DIABETIC KK-CA(Y) MICE

The effect of insulin on glucose and 2-deoxyglucose uptake into isolated diaphragm was investigated in genetically diabetic KK-CA(y) mice, and in part in alloxan-treated mice. Concentration-response curves of insulin for glucose uptake (8.3 mM in vitro) for 1 h were shifted to the left in two kinds of diabetic model mice. Insulin-stimulated glucose uptake was biphasic; it was high 1 week, and returned to the normal level 4 weeks, after alloxan injection despite high blood glucose levels. Insulin-stimulated glucose uptake was the same at higher glucose levels (25 mM) as at 8.3 mM glucose for 1 h, despite an increase in basal glucose uptake (without insulin) in KK-CA(y) mice. Insulin-receptor kinase activity in diabetic KK-CA(y) mouse diaphragm also changed biphasically as the glucose concentration increased: an increase at 8.3 mM, but no increase at 16.7 mM or 25.0 mM glucose for 3 h-pretreatment including 1 h-insulin treatment. These results suggest that although the initial state of diabetes enhances insulin action, the prolonged hyperglycemia rather suppressed the insulin action in vivo.