Diabetic state-induced modification of insulin-stimulated, glucose uptake into and kinase activity in, the diaphragm muscle of genetically diabetic KK-CAy mice.
The effect of insulin on glucose and 2-deoxyglucose uptake into isolated diaphragm was investigated in genetically diabetic KK-CAy 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-CAy mice. Insulin-receptor kinase activity in diabetic KK-CAy 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.
Kimura
M
M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Naitoh
T
T
Kobayashi
S
S
Kimura
I
I
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D003964:Diaphragm / Q000187:drug effects / Q000201:enzymology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009132:Muscles / Q000187:drug effects / Q000201:enzymology*; D010770:Phosphotransferases / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D003847:Deoxyglucose; D010770:Phosphotransferases; D005947:Glucose