Sensitivity of β-Cells to Streptozotocin in Lean and Obese Rats

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Abstract
Two experiments have tested the hypothesis that pancreatic sensitivity to diabetogenic agents may be increased by obesity. In the first experiment, lean and hypothalamic obese (VMH) rats were injected with 15, 25, or 35 mg/kg of streptozotocin. The VMH-obese rats showed a dose-related rise in blood glucose but the lean rats only showed a rise in glucose with the highest dose. All obese rats which received 35 mg/kg of streptozotocin died of ketoacidosis, and 3 of the 6 obese rats receiving 25 mg/kg of streptozotocin became diabetic (2 with ketoacidosis). Among the lean rats, only 3 became mildly diabetic. Serum insulin levels were decreased significantly with 25 and 35 mg/kg one week after streptozotocin in the obese rats, but there was no change in the lean rats. In the second experiment, lean rats received a single dose of streptozotocin (25 mg/kg) one week before hypothalamic lesions. Animals were subsequently divided into four groups (VMH-high fat diet: VMH-low fat diet: Sham-high fat diet: Sham-low fat diet). The VMH-obese rats fed a high fat diet showed a progressive rise in glucose. All groups except the sham-operated rats fed the low fat diet, showed impaired glucose tolerance. After 7 weeks, an additional 5 mg of streptozotocin was given to each rat. The subsequent rise of serum glucose was weight-related. Diabetes developed in 5 of the 6 obese rats on the high fat diet, in 3 of the obese rats on the low fat diet, and in 2 of the sham-operated rats on the high fat diet. None of the lean rats became diabetic. These results suggest that the pancreatic β-cells may be more susceptible to a diabetogenic agent, such as streptozotocin after the development of obesity than the β-cells of lean animals.