The contribution of hyperglycaemia and hypoinsulinaemia to the insulin resistance of streptozotocin-diabetic rats.
The relative contribution of hyperglycaemia and hypoinsulinaemia was evaluated in rats made diabetic by streptozotocin administration. Four groups of rats were studied: untreated normal rats; streptozotocin-diabetic; streptozotocin-diabetic treated with phlorizin (0.4 mg/kg body weight per day); streptozotocin-diabetic mildly treated with insulin (0.7 IU/day). In all groups, insulin action (responsiveness) was assessed with the euglycaemic (5.3 mmol/l) hyperinsulinaemic (524 mU/l) clamp technique combined with 3H-2-deoxy-D-glucose method, enabling determination of the glucose utilization index in various tissues. Responsiveness of the overall glucose utilization process to insulin was reduced by 28% in streptozotocin-diabetic rats (12.0 +/- 1.2 vs 16.5 +/- 0.6 mg.kg-1.min-1, p less than 0.001). This was associated with a significant reduction (p less than 0.05) in the glucose utilization index in all muscles studied (average = 17.0 vs 32.1 ng.mg of tissue-1.min-1), in the heart (19.6 vs 39.5 ng.mg-1.min-1), brown adipose tissue (98.9 vs 178.0 ng.mg-1.min-1), skin (6.4 vs 13.1 ng.mg-1.min-1). Phlorizin treatment normalized plasma glucose levels without affecting those of insulin, and restored overall glucose utilization to normal (16.6 +/- 1.0 mg.kg-1.min-1). This normalization was accompanied by a normalization of the glucose utilization index in all muscle types studied (29.2 ng.mg-1.min-1), in the heart (50.0 ng.mg-1.min-1), brown adipose tissue (157.2 ng.mg-1.min-1), and skin (10.0 ng.mg-1.min-1). White adipose tissue, brain and gut were not affected.(ABSTRACT TRUNCATED AT 250 WORDS)
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Cattedra di Malattie del Ricambio, Università di Padova, Italy.
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Tiengo
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Del Prato
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Jeanrenaud
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D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004435:Eating; D005215:Fasting; D005947:Glucose / Q000378:metabolism*; D006943:Hyperglycemia / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008099:Liver / Q000378:metabolism*; D008297:Male; D009928:Organ Specificity; D051381:Rats; D011924:Rats, Zucker; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D003847:Deoxyglucose; D005947:Glucose