We studied glucagon and insulin binding to isolated hepatocyte receptors in Wistar-Furth (WF) and Sprague-Dawley (SD) rats, using '251-labeled hormones. Hepatocytes from WF rats bound more glucagon than hepatocytes from SD rats. There were no differences in insulin binding. These observations prompted us to investigate other strain differences. Fasting and nonfasting serum glucose, glucagon, insulin, and growth hormone were measured. WF animals had a lower fasting glucose and higher fasting glucagon than SD animals, while SD rats had higher nonfasting insulin levels and a higher hepatic glycogen content. Total hepatic glucose production in response to glucagon ( M ) was greater in WF than in SD rats, while glucagon-stimulated gluconeogenesis from alanine was the same in the two groups of animals. We concluded that the decreased glucagon binding does not play a significant role in the maintenance of serum glucose or in the gluconeogenetic response glucagon, and that neither these responses nor the serum glucagon levels appears to be correlated with the number of glucagon receptors. We conclude further that different animal strains of the same species may differ in their biologic responses. Downloaded from 32-37, 1985. tuitary gland: Effect of age, sex, and hormonal state. Endocrinology (Baltimore) 81: 195-204, 1967. 10. Zahlten RN, Kneer NM, Stratman FW, Lardy HA. The influence of ammonium and calcium ions on

The effect of increased levels of growth hormone on glucagon binding by isolated hepatocytes and on the cellular cyclic AMP response to glucagon was evaluated in rats bearing growth hormone-secreting tumor (Mt-T-W 15) and in rats treated with rat growth hormone. An increased binding, due to an increased number of receptors, was observed in both groups of animals. Glucagon binding did not correlate with plasma glucagon levels, suggesting a failure of down regulation, possibly due to an effect of growth hormone and insulin on the number of receptors. Tumor-bearing and growth hormone-treated rats had larger hepatocytes so that, when hormone binding was expressed in terms of square micrometer of membrane surface, it appeared decreased. When the tumor was removed the increase in the number of glucagon receptors per cell persisted, even though the average cell size returned toward normal. It is suggested that this retention of the receptors may have been the result of continuing hyperinsulinism. Basal cAMP levels were elevated in hepatocytes of tumor-bearing and growth hormone-treated animals, possibly due to cell hypertrophy. On the other hand, the maximum cAMP response to glucagon was not altered by the experimental procedures. A negative effect of insulin on cAMP accumulation may explain this apparent paradox, Indeed, hepatocytes isolated from rats following tumor removal, but with continuing hyperinsulinemia, had a lower maximum cAMP response, even though the glucagon binding per cell or per unit of cell surface Was increased.