Dietary control of circadian variations in serum insulin, glucagon and hepatic cyclic AMP

The effect of a high-protein diet (favoring hepatic glucose production) and of a high-carbohydrate diet (favoring glucose utilization) on the concentration of insulin and glucagon in the blood and on adenosine 3',5'-cyclic monophosphate (cyclic AMP) in the liver was investigated during a 24-hour cycle in rats. Feeding a high-protein diet resulted within 3 hours in an increase in the concentration of insulin (+100%) and glucagon (+220%). Whereas feeding a high-carbohydrate diet again induced a rise in insulin (+140%), no alterations in glucagon were observed. Hepatic cyclic AMP oscillated up or down under the protein or carbohydrate diet, respectively. A correlation between the insulin/glucagon molar ratio and the concentration of hepatic cyclic AMP was found. Protein-bound cyclic AMP, an indicator of protein kinase activation, corresponded closely to total cyclic AMP tissue concentration. The activity of a gluconeogenic key enzyme, P-enolpyruvate carboxykinase oscillated in parallel to hepatic cyclic AMP. Our data demonstrate that the protein and carbohydrate content of the diet determines the shape of circadian variation of hepatic cyclic AMP, insulin and glucagon.