Effects of 2-deoxy-D-glucose and insulin on plasma glucose levels and behavioral thermoregulation of toads

The present study was designed to test the hypothesis that hypoglycemia induces hypothermia in ectotherms and to elucidate the mechanisms responsible for behavioral hypothermia. Behavioral hypothermia is a stress response that occurs in organisms ranging from protozoans to mammals, but very little is known about the cellular mechanisms involved. Toads equipped with a temperature probe were tested in a thermal gradient (10-40 degrees C). Insulin was used to reduce plasma glucose levels, and an inhibitor of glucose utilization, 2-deoxy-D-glucose (2-DG), was used to cause intracellular glucopenia. Insulin injections into the dorsal lymph sac caused significant reductions of both plasma glucose levels and body temperature. To determine if the response was mediated by extracellular glucose receptors or an intracellular mechanism. 2-DG was also injected into the lymph sac. 2-DG caused a similar drop in body temperature and a marked increase in plasma glucose. To assess the role of central thermoregulatory mechanisms, a smaller dose of 2-DG was injected into the fourth cerebral ventricle or the lymph sac. Intracerebroventricular injection of 2-DG caused a decrease in body temperature despite elevated circulating glucose levels, whereas injection into the lymph sac caused no significant change. The data indicate that exclusion of glucose from central rather than peripheral sites plays a major role in the hypoglycemia-induced behavioral hypothermia and that intracellular mechanisms rather than extracellular glucose receptors are involved in this response. Hypothermia may be a beneficial response to hypoglycemia in toads because it dampens cellular oxidative demands during glucose deprivation.