Effect of pharmacological suppression of insulin secretion on tissue sensitivity to insulin in subjects with moderate obesity.
After informed consent we studied effect of pharmacological suppression of insulin secretion on tissue sensitivity to insulin in eight subjects with moderate obesity (relative body weight 133 +/- 6 per cent). Glucose tolerance (100 g oGTT) and insulin sensitivity were studied on two separate days before and after treatment with 500 mg diazoxide/d for a period of 4 d. Insulin sensitivity was determined by means of a 1-h priming dose-constant insulin infusion technique (two 30-min periods of 8 and 16 mU/kg, insulin MC-Actrapid, initiated by a start injection of 1 and 2 mU/kg, respectively). The relative decrease of plasma glucose and nonesterified fatty acid concentration at comparable steady-state insulin levels has been taken as an estimate of body sensitivity to insulin. Diazoxide treatment resulted in a significant suppression of glucose-stimulated early (insulin area 0-30 min) (P less than 0.05), late (insulin area 30-120 min) (P less than 0.01) and total insulin response (insulin area 0-120 min) (P less than 0.01) as well as a mild deterioration of glucose tolerance. Insulin sensitivity increased by about 50 per cent in comparison to the pretreatment value. Similarly, there was a marked increase of the antilipolytic effect of insulin after short-term treatment with diazoxide (P less than 0.05). The results support the concept that decreased sensitivity to insulin in obesity may be secondary due to hyperinsulinaemia.
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003981:Diazoxide / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D003981:Diazoxide