Moderate insulinopenia can cause insulin antagonism.
Profound insulin deficiency can cause insulin antagonism. To assess whether more modest insulinopenia can also cause insulin antagonism, male Sprague-Dawley and female obese (fa/fa) Zucker rats received streptozotocin injections (20, 30 or 40 mg/kg) or citrate buffer alone. After 1 and 2 weeks, the animals underwent glucose (0.5 g/kg) and insulin (0.2 U/kg)-glucose (0.7 mg/kg) tolerance tests, respectively, after an overnight fast. In the Sprague-Dawley rats: (a) basal glucose concentrations were significantly increased in the 40 mg/kg group; (b) glucose-induced insulin responses were significantly decreased in the 30 and 40 mg/kg groups; (c) glucose disappearance rates after glucose alone were significantly decreased in the 40 mg/kg group; and (d) glucose disappearance rates after insulin and glucose were significantly decreased in both the 30 and 40 mg/kg group. All obese Zucker rats injected with 30 and 40 mg/kg died within the first week with marked hyperglycemia. In the 20 mg/kg groups: (a) basal glucose levels were significantly elevated; (b) glucose disappearance rates and insulin responses were significantly decreased; (c) glucose disappearance rates after insulin and glucose were 20% lower than in the control rats but the difference did not reach statistical significance. In conclusion, Zucker rats are much more sensitive to streptozotocin than Sprague-Dawley rats. In the Sprague-Dawley strain, a modest insulin deficiency is associated with insulin antagonism. Since these rats treated with low doses of streptozotocin are characterized by decreased glucose-induced insulin secretion and insulin antagonism, they may serve as an appropriate model for type 2 diabetes mellitus.
Shen
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DC
Department of Medicine, Cedars-Sinai Medical Center, University of California, Los Angeles 90048.
Davidson
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MB
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007329:Insulin Antagonists / Q000502:physiology*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011924:Rats, Zucker; D013045:Species Specificity
D007328:Insulin; D007329:Insulin Antagonists; D005947:Glucose