The Hypothermia of Hypoglycemia: Studies with 2-Deoxy-D-Glucose in Normal Human Subjects and Mice

An inhibitor of glucose utilization, 2-deoxy-D-glucose (2-DG) was employed to study the hypothermia of hypoglycemia. After 2-DG infusions, rectal temperatures in normal human subjects fell to nadir levels averaging 1.1°C below base-line values in two to 2.5 hours coincident with maximal increases of plasma growth hormone. Temperatures remained below basal values for six hours in the face of increases in plasma glucose and insulin, and urinary catecholamines. The findings indicate that the hypothermia is conditioned by intracellular glucopenia rather than the availability of circulating glucose or glucoregulatory hormones. To assess the role of central thermoregulatory mechanisms, 2-DG was injected into tail veins or cerebral ventricles of conscious mice. Although rectal temperatures fell with either route, hypothermic potencies were approximately fivefold greater with intracerebral administration. Thus, exclusion of glucose from central rather than peripheral sites plays the major part in the hypothermia of hypoglycemia. Such modulations of temperature may provide a means for dampening cellular oxidative demands during glucose deprivation.