INFLUENCE OF OBESITY AND DIABETES IN THE MONKEY ON INSULIN AND GLUCAGON BINDING TO LIVER MEMBRANES

Longitudinal studies of the laboratory rhesus monkey have revealed a syndrome of carbohydrate intolerance in those that approach or become middle aged and spontaneously obese. In addition, hyperinsulinemia is present, indicating insulin resistance. In an attempt to understand the mechanism of this hormonal resistance, insulin and glucagon binding to partially purified liver membranes obtained from nonobese, nondiabetic monkeys and obese animals with or without diabetes was measured. When expressed on the basis of membrane protein content or 5′-nucleotidase activity, insulin binding was significantly reduced in both groups of obese animals as compared to age-matched controls. This impairment of insulin binding was due to decreased numbers of available receptor sites and not to a change in affinity, which was slightly increased in the obese. Glucagon binding was also reduced in obesity, but the difference from normal was significant only in the group with diabetes and established hyperglucagonemia. Significant inverse relationships between fasting plasma insulin concentration and hormone binding (insulin, P < 0.01; glucagon, P < 0.05) were observed. In contrast, no correlation was noted between plasma glucagon and the binding of either hormone. Diminished insulin and glucagon binding was also present in livers from two monkeys with hypothalamic obesity. These animals were heavier than those with spontaneous obesity and had plasma glucagon levels lower than normal. Although not confirmatory, the data are compatible with the concept that reduced hepatic insulin receptors are involved in the insulin resistance of a primate model which has many similarities to human obesity and nonketotic diabetes. © 1979 by The Endocrine Society.