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Diabetes 53:67-73, 2004
© 2004 by the American Diabetes Association, Inc.
Metabolic Pathways That Mediate Inhibition of Hypothalamic Neurons by Glucose
1 Fishberg Center for Neurobiology, Neurobiology of Aging Laboratories, and Department of Geriatrics Mount Sinai School of Medicine, New York, New York
2 Laboratory of Neurobiology, The Rockefeller University, New York, New York
Neurons in the ventromedial hypothalamus mediate some counterregulatory responses to hypoglycemia and 2-deoxyglucose, but the mechanisms that mediate these responses to glucose are unclear. In the present study, ventromedial hypothalamus neurons were identified on the basis of their inhibition by the transition from 5 to 20 mmol/l glucose. Tolbutamide, which activates glucose-stimulated neurons, failed to inhibit or activate glucose-inhibited neurons. Inhibitors of glucose transport and glycolysis, in particular by the glucokinase inhibitor glucosamine, blocked the effect of glucose on glucose-inhibited neurons. Furthermore, the glucose-inhibited neurons were activated by 2-deoxyglucose, which also activates counterregulatory responses. Conversely, glucose-inhibited neurons were inhibited by glycolytic metabolites, including lactate, but not by pyruvate. These data indicate that hypoglycemia induces electrical activity in glucose-inhibited neurons by attenuating glycolysis in those neurons. Thus, counterregulatory failure could be due to relatively enhanced glycolysis in glucose-stimulated neurons during hypoglycemia and attenuation of glycolysis in glucose-inhibited neurons might reverse counterregulatory failure.
Address correspondence and reprint requests to Dr. Charles V. Mobbs, Neurobiology of Aging Laboratories, Box 1639, Mt. Sinai School of Medicine, 1425 Madison Ave., New York, NY 10029-6574. E-mail: charles.mobbs{at}mssm.edu
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