Resistance of obese and non-obese, spontaneously hypertensive rats to alloxan-induced diabetes.

Male, 5 months old, massively obese, spontaneously hypertensive rats (Obese/SHR) were given 10 mg alloxan/100 g b.w., s.c., to induce diabetes. Control Obese and non-obese/SHR were given saline. Insulin therapy was withheld. All of the animals were killed at 6 months of age. Alloxan caused a slight but statistically significant increase in blood pressure, pituitary and adrenal glandular hyperplasia, hyperlipidemia, hyperglycemia, and increased BUN levels. The giant sized islets of Langerhans in Obese/SHR showed only partial degranulation of the insulin-producing beta cells concomitant with residual but apparently adequate blood insulin levels, whereas the islets of non-obese/SHR exhibited virtually total beta cell degranulation and only trace amounts of blood insulin. The alloxanized, non-obese rats were severely emaciated; the alloxanized Obese/SHR maintained their obesity. Alloxan-treated, Obese and non-obese/SHR manifested gross and microscopic degenerative changes suggesting acceleration of the normal aging process. The genetically-programmed pathogenesis of diabetes, obesity, hypertension, and Cushingoid pathophysiology of Obese/SHR may be due to hyperadrenocorticism.