IN-VIVO INSULIN ACTION IN NORMAL AND STREPTOZOTOCIN-INDUCED DIABETIC RATS

Models studying in vivo insulin animal action usually employ single-us e anesthetized animals, mainly for technical reasons. We developed a m odification of the euglycemic insulin clamp technique and used it to r epeatedly assess in vivo insulin effects in awake streptozotocin-induc ed diabetic rats, and in weight- and/or age-matched controls. Permanen t catheters implanted into the left carotid artery and the right jugul ar vein were used for miniature blood sampling (20 mu l) and recycling . Insulin was infused at 1, 2, 3, 15, and 30 mU/kg.min. Plasma insulin and C-peptide levels and glucose utilization rate were measured at bl ood glucose levels of 100 mg/dl. Diabetes was associated with diminish ed elevation of plasma C-peptide and insulin levels after ad lib feedi ng, 50% decreased (p < 0.005) insulin sensitivity, 31% decreased (p < 0.001) insulin responsiveness, and unchanged insulin clearance rates. Thus, using repeated clamps of the same rat over a prolonged period of time, we demonstrate that diabetes is associated with unchanged clear ance but decreased sensitivity and responsiveness to insulin.