The daily rhythm in plasma glucagon concentrations in the rat is modulated by the biological clock and by feeding behavior

Plasma glucose concentrations display a daily rhythm generated by the hypothalamic biological clock, located in the suprachiasmatic nucleus (SCN). How the SCN orchestrates this rhythm is unknown. Because glucagon stimulates hepatic glucose production, we hypothesized that if glucagon has a daily rhythm, then it may be responsible for the glucose rhythm. From hourly blood samples, we determined daily glucagon concentrations for intact and SCN-lesioned rats. Intact ad libitum-fed rats showed a clear daily glucagon rhythm, and fasting resulted in an even more pronounced rhythm. It is interesting that a decrease in glucagon concentrations, instead of the expected increase, occurred already shortly after food removal. Toward the start of the active period, a peak in glucagon levels occurred, with concentrations similar to those measured in ad libitum-fed rats. SCN lesions abolished rhythmicity in plasma glucagon profiles. Scheduled-fed rats showed meal-induced glucagon peaks but also a daily rhythm in basal premeal glucagon concentrations. Plasma glucose concentrations of ad libitum- and scheduled-fed rats, however, were similar. In conclusion, feeding and the biological clock control 24-h plasma glucagon concentrations. In fed rats, glucagon is not responsible for the daily glucose rhythm. During fasting, however, glucagon may contribute to energy mobilization when the activity period starts.