Physiologic and cellular insulin action in a glucose-intolerant model of type 2 (non-insulin-dependent) diabetes in rats.
A B-cell-deficient model for Type 2 (non-insulin-dependent) diabetes mellitus has been investigated with regard to insulin action at the cellular level. Two-day-old male Sprague Dawley rats were injected with streptozotocin (90 mg/kg) or citrate buffer. At 6 weeks streptozotocin-treated animals were hyperglycaemic and exhibited glucose intolerance, e.g. at 45 min post-glucose (1.5 g/kg) the change in serum glucose level from baseline was 6 +/- 7 mg% in control rats vs. 212 +/- 18 mg% for the streptozotocin-treated rats. Basal activity and insulin action in isolated adipocytes, as estimated by 2-deoxyglucose uptake and glucose metabolism, were not influenced by streptozotocin treatment. For example, uptake of 0.1 mmol/1 2-deoxyglucose at 1000 microU insulin/ml was 58 +/- 8 pmol/10(5) cells min-1 vs 54 +/- 6 pmol for adipocytes isolated from experimental vs. control animals. Although serum insulin levels in streptozotocin-treated rats were significantly decreased (p less than 0.05), there was no difference in insulin receptor number or affinity. Glucose intolerance present in this model is similar to that in Type 2 diabetes. However, concomitant insulin intolerance was not observed. Taken together with our findings of unaltered insulin action at the cellular level, this suggests that the pathogenesis of insulin resistance is not dependent on glucose intolerance. Moreover, this hyperglycaemic model is responsive to oral hypoglycaemic agents and can be used to establish their direct effects on physiologic and cellular insulin action.
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism; D014042:Tolazamide / Q000627:therapeutic use
D001786:Blood Glucose; D007328:Insulin; D014042:Tolazamide; D011972:Receptor, Insulin; D005947:Glucose