Effects of endogenous glucagon on glucose kinetics in shivering dogs

Intravenous infusion of D-[3-3H]glucose at a constant rate was used to measure glucose production (rate of appearance, Ra) and utilization (rate of disappearance, Rd) in normal overnight-fasted dogs exposed to either neutral (TaN = +25 degrees C) or cold (TaC = -21 degrees C) ambient temperature. At TaC the metabolic rate was 4.1 times greater than at TaN and the dogs remained normothermic under both conditions. During control periods, cold exposure provoked a 2.2 times increase in hepatic Ra while plasma glucagon remained unaffected. Between two control periods somatostatin (1 microgram.kg-1.min-1 iv) and insulin (0.5 mU.kg-1.min-1 intraportal) were infused in such a manner that plasma insulin remained fairly constant at basal levels while glucagon dropped by 51% (TaN) and 66% (TaC), these percentages being not significantly different. This selective glucagon deficiency resulted in a 24% (TaN) and 30% (TaC) reduction in plasma glucose concentration, due to a 23% (TaN) and 25% (TaC) reduction in glucose production. There was a significant (r = 0.82, P less than 0.01) correlation between the control Ra and the reduction induced by the glucagon deficiency. At TaN and TaC, two significant parallel relationships were found between hepatic Ra and plasma glucagon concentration suggesting that glucagon has a modulatory effect on more fundamental mechanisms triggered by the cold-increased metabolic needs.