Hyperinsulinism in Mice with Genetically Determined Obesity

Blood glucose, plasma insulin and pancreatic insulin content in obese mice (obob) have been measured at various ages and compared to results from normal mice. Plasma insulin of obese mice was 8- to 30-fold higher than controls at all ages and irrespective of concurrent hyperglycemia. Pancreatic insulin of obese mice was lower than in controls at 6 weeks, equaled results for controls at 7 weeks, and exceeded controls at 9 weeks and thereafter. Immunoassay of plasma and pancreatic insulin of obese mice gave curves that paralleled those for insulin of normal mice. The hypoglycemic effect of pancreatic insulin of obese mice was commensurate with its immunoreactive potency. Intraperitoneal glucose administration caused no further rise in plasma insulin of obese mice. Endogenous glycemia caused a greater rate of insulin secretion in obese mice than did acute or sustained hyperglycemia in normal mice. It is suggested that hyperinsulinism in obese mice may be due to a primary abnormality in islet cell function rather than to insulin resistance alone. (Endocrinology 84: 386, 1969)