Enhanced uptake of insulin and glucagon by liver in rats adapted to a high protein diet.

The regulatory role of the liver with regard to circulating concentrations of insulin and glucagon was investigated in rats adapted to high carbohydrate (HC) or high protein (HP) diets, during the period of maximal nutrient absorption. In rats fed HC diet, high secretion of insulin into portal vein in conjunction with low hepatic uptake elicited systemic hyperinsulinemia. In rats fed HP diet, both insulin and glucagon were secreted in large amounts, but hormone removal by the liver was greater than in rats fed the HC diet. Hepatic fractional extraction was higher for insulin than for glucagon: systemic insulin/glucagon ratio was, therefore, lower than the portal insulin/glucagon ratio. Binding of insulin and glucagon to hepatocyte cell membranes was lower in rats fed HP diet than in those fed the HC diet: this could correspond in vivo to a higher rate of internalization of occupied receptors since affinities of the receptors were unchanged. The results indicate that in rats adapted to HP diets the liver undergoes specific adaptations for regulation of peripheral insulin/glucagon levels, along with its role of target tissue for these hormones.