Glucagon and the paraventricular hypothalamus: modulation of energy balance.

The effects of glucagon injections (25, 100 and 200 ng) into the paraventricular nucleus of the hypothalamus (PVN) were investigated in an open-circuit calorimeter. Wistar rats were tested, with no food available during the tests. High doses of glucagon (100 and 200 ng) produced small and short-lasting increases in energy expenditure. The independence of these changes from changes in locomotor activity suggests that the thermogenesis represents a primary modulation and is not secondary to increased locomotion. All three doses of glucagon produced long-lasting and dose-related increases in respiratory quotient which were unrelated to any changes in locomotor activity. As with the changes in energy expenditure, this dissociation indicates that the effects are not secondary to changes in locomotor activity. These data constitute the first evidence that glucagon in the PVN modulates the metabolic parameters central to energy balance. In separate experiments, the three doses of glucagon increased blood glucose concentration over a one hour period, but they did not affect food and water intake and body weight over 24 h. These findings suggest that glucagon normally acts on the PVN in conditions of increased body fat to initiate autonomic mechanisms which increase glycemic levels, thermogenesis and carbohydrate utilization. These data constitute the first direct evidence for the involvement of the PVN in the regulation of energy balance by glucagon. The main effect of glucagon in the PVN is anabolic in that it increases dependence on carbohydrates as an energy substrate which results in a sparing of fat reserves.