Hepatic and peripheral insulin resistance following streptozotocin-induced insulin deficiency in the dog.
Insulin resistance and insulin deficiency are both present in many patients with diabetes mellitus. We tested the hypothesis that insulin resistance can evolve from a primary lesion of the beta-cell secretory function. Insulin-mediated glucose uptake (insulin clamp), endogenous glucose production, and glucose-stimulated insulin secretion (hyperglycemic clamp) were measured in awake dogs before and four to six weeks after streptozotocin-induced diabetes mellitus. Streptozotocin (30 mg/kg) resulted in a significant rise in the mean fasting plasma glucose concentration from 104 +/- 2 mg/100 mL to 200 +/- 34 mg/100 mL, (P less than 0.05), and a slight decrease in the mean fasting plasma insulin concentration (from 21 +/- 2 microU/mL to 15 +/- 2 microU/mL). Under conditions of steady-state hyperglycemia (+75 mg/100 mL hyperglycemic clamp, insulin secretion was reduced by 75% in the streptozotocin-treated dogs (P less than 0.025), and the total amount of glucose metabolized decreased from 13.56 +/- 1.04 to 4.74 +/- 0.70 mg/min X kg (P less than 0.001). In the postabsorptive state, endogenous glucose production was slightly, although not significantly, higher in the diabetic dogs (3.05 +/- 0.46 v 2.51 +/- 0.22 mg/min . kg), while the glucose clearance rate was 35% lower (P less than 0.001). When the plasma insulin concentration was increased to approximately 45 microU/mL (insulin clamp) while holding plasma glucose constant at the respective fasting levels (99 +/- 1 and 186 +/- 30 mg/100 mL), endogenous glucose production was completely suppressed in control dogs but suppressed by only 51% (1.46 +/- 0.37 mg/min . kg, P less than 0.025) in diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D004285:Dogs; D005215:Fasting; D005947:Glucose / Q000378:metabolism; D006943:Hyperglycemia / Q000097:blood; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000503:physiopathology; D008099:Liver / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D010477:Perfusion; D011972:Receptor, Insulin / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D011972:Receptor, Insulin; D005947:Glucose