Hypothalamic glucose sensor: similarities to and differences from pancreatic beta-cell mechanisms

• Published in: Diabetes (New York, N.Y.) Vol. 48; no. 9; pp. 1763 - 1772
• Main Authors: YANG, X.-J, KOW, L.-M, FUNABASHI, T, MOBBS, C. V
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.09.1999
• Subjects: Animals; Biological and medical sciences; Cerebral Cortex - cytology; Cerebral Cortex - metabolism; Deoxyglucose - pharmacology; Electrodes; Endocrine pancreas; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Glucose - pharmacology; Glycolysis - drug effects; Hypoglycemic Agents - pharmacology; Hypothalamus, Middle - cytology; Hypothalamus, Middle - metabolism; In Vitro Techniques; Iodoacetic Acid - pharmacology; Male; Morphology. Functional localizations; Neurons - metabolism; Phlorhizin - pharmacology; Pyruvic Acid - pharmacology; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Stimulation, Chemical; Vertebrates: endocrinology; Rat; Langerhans islet; Rodentia; Central nervous system; Glucose; Hypothalamus; Vertebrata; Sensitivity; Mammalia; Neuron; B-Cell; Chemosensitivity; Comparative study; Brain (vertebrata); Endocrine pancreas
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.48.9.1763

Hypothalamic glucose sensor: similarities to and differences from pancreatic beta-cell mechanisms. X J Yang , L M Kow , T Funabashi and C V Mobbs Fishberg Center for Neurobiology, and Department of Geriatrics, Mount Sinai School of Medicine, New York, New York 10029-6574, USA. Abstract Glucose-responsive neurons in the ventromedial hypothalamus (VMH) are stimulated when glucose increases from 5 to 20 mmol/l and are thought to play an essential role in regulating metabolism. The present studies examined the role of glucose metabolism in the mechanism by which glucose-responsive neurons sense glucose. The pancreatic, but not hepatic, form of glucokinase was expressed in the VMH, but not cerebral cortex, of adult rats. In brain slice preparations, the transition from 5 to 20 mmol/l glucose stimulated approximately 17% of the neurons (as determined by single-cell extracellular recording) from VMH but none in cortex. In contrast, most cells in both VMH and cortex were silent below 1 mmol/l and active at 5 mmol/l glucose. Glucosamine, 2-deoxyglucose, phloridzin, and iodoacetic acid blocked the activation of glucose-responsive neurons by the transition from 5 to 20 mmol/l glucose. Adding 15 mmol/l mannose, galactose, glyceraldehyde, glycerol, and lactate to 5 mmol/l glucose stimulated glucose-responsive neurons. In contrast, adding 15 mmol/l pyruvate to 5 mmol/l glucose failed to activate glucose-responsive neurons, although pyruvate added to 0 mmol/l glucose permitted neurons to maintain activity. Tolbutamide activated glucose-responsive neurons; however, diazoxide only blocked the effect of glucose in a minority of neurons. These data suggest that glucose-responsive neurons sense glucose through glycolysis using a mechanism similar to the mechanism of pancreatic beta-cells, except that glucose-responsive neurons are stimulated by glycerol and lactate, and diazoxide does not generally block the effect of glucose.