Brain glucose-sensing mechanisms: Ubiquitous silencing by aglycemia vs. hypothalamic neuroendocrine responses

Charles V. Mobbs, Lee Ming Kow, Xue Jun Yang

Research output: Contribution to journalReview articlepeer-review

89 Scopus citations

Abstract

Interest in brain glucose-sensing mechanisms is motivated by two distinct neuronal responses to changes in glucose concentrations. One mechanism is global and ubiquitous in response to profound hypoglycemia, whereas the other mechanism is largely confined to specific hypothalamic neurons that respond to changes in glucose concentrations in the physiological range. Although both mechanisms use intracellular metabolism as an indicator of extracellular glucose concentration, the two mechanisms differ in key respects. Global hyperpolarization (inhibition) in response to 0 mM glucose can be reversed by pyruvate, implying that the reduction in ATP levels acting through ATP-dependent potassium (K-ATP) channels is the key metabolic signal for the global silencing in response to 0 mM glucose. In contrast, neuroendocrine hypothalamic responses in glucoresponsive and glucose-sensitive neurons (either excitation or inhibition, respectively) to physiological changes in glucose concentration appear to depend on glucokinase; neuroendocrine responses also depend on K-ATP channels, although the role of ATP itself is less clear. Lactate can substitute for glucose to produce these neuroendocrine effects, but pyruvate cannot, implying that NADH (possibly leading to anaplerotic production of malonyl-CoA) is a key metabolic signal for effects of glucose on glucoresponsive and glucose-sensitive hypothalamic neurons.

Original languageEnglish
Pages (from-to)E649-E654
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume281
Issue number4 44-4
DOIs
StatePublished - 2001

Keywords

  • Adenosine triphosphate-dependent potassium channel
  • Glucokinase
  • Hypoglycemia
  • Obesity
  • Ventromedial hypothalamus

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