Plasma glucagon, glucose, and free fatty acid concentrations and secretion during prolonged hypothermia in rats

Impairment of metabolic substrate mobilization and utilization may be a factor limiting survival in hypothermia. Using a newly developed technique for maintaining stable low body temperature (Tb), substrate profiles and their regulation by glucagon were examined in hypothermic rats (Tb 19 +/- 0.3 degrees C) over 20 h. During cooling, plasma glucagon, glucose, and free fatty acid (FFA) concentrations increased significantly (536 +/- 55 pg/ml, 304 +/- 26 mg/100 ml, and 844 +/- 81 mueq/l, respectively). Plasma glucagon and glucose concentrations continued to increase up to 8 h (peaks 810 +/- 103 pg/ml and 451 +/- 33 mg/100 ml, respectively) and remained high throughout the rest of the hypothermic period. FFA concentrations decreased steadily during the hypothermic period. Exogenous glucagon (20 micrograms/kg) induced significant increases in plasma glucose (+129 +/- 31 mg/100 ml) and FFA concentrations (+351 mueq/l) at 2 h but had no effect at 15 h of hypothermia. In vitro evaluation of pancreatic alpha-cell function indicated that glucagon secretion is independent of temperature between 37 and 19 degrees C. Our data indicate that hypothermia is characterized by a disturbed substrate metabolism, which is likely due to an imbalance in pancreatic alpha- and beta-cell function and a time-dependent decrease in tissue sensitivity to glucagon. These deleterious changes may limit survival in hypothermia.