Synaptic Glutamate Release by Ventromedial Hypothalamic Neurons Is Part of the Neurocircuitry that Prevents Hypoglycemia

Qingchun Tong, ChianPing Ye, Rory J. McCrimmon, Harveen Dhillon, Brian Choi, Melissa D. Kramer, Jia Yu, Zongfang Yang, Lauryn M. Christiansen, Charlotte E. Lee, Cheol Soo Choi, Jeffrey M. Zigman, Gerald I. Shulman, Robert S. Sherwin, Joel K. Elmquist, Bradford B. Lowell

Research output: Contribution to journalArticle

238 Scopus citations

Abstract

The importance of neuropeptides in the hypothalamus has been experimentally established. Due to difficulties in assessing function in vivo, the roles of the fast-acting neurotransmitters glutamate and GABA are largely unknown. Synaptic vesicular transporters (VGLUTs for glutamate and VGAT for GABA) are required for vesicular uptake and, consequently, synaptic release of neurotransmitters. Ventromedial hypothalamic (VMH) neurons are predominantly glutamatergic and express VGLUT2. To evaluate the role of glutamate release from VMH neurons, we generated mice lacking VGLUT2 selectively in SF1 neurons (a major subset of VMH neurons). These mice have hypoglycemia during fasting secondary to impaired fasting-induced increases in the glucose-raising pancreatic hormone glucagon and impaired induction in liver of mRNAs encoding PGC-1α and the gluconeogenic enzymes PEPCK and G6Pase. Similarly, these mice have defective counterregulatory responses to insulin-induced hypoglycemia and 2-deoxyglucose (an antimetabolite). Thus, glutamate release from VMH neurons is an important component of the neurocircuitry that functions to prevent hypoglycemia.

Original languageEnglish (US)
Pages (from-to)383-393
Number of pages11
JournalCell Metabolism
Volume5
Issue number5
DOIs
StatePublished - May 9 2007

Keywords

  • HUMDISEASE
  • MOLNEURO

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Tong, Q., Ye, C., McCrimmon, R. J., Dhillon, H., Choi, B., Kramer, M. D., Yu, J., Yang, Z., Christiansen, L. M., Lee, C. E., Choi, C. S., Zigman, J. M., Shulman, G. I., Sherwin, R. S., Elmquist, J. K., & Lowell, B. B. (2007). Synaptic Glutamate Release by Ventromedial Hypothalamic Neurons Is Part of the Neurocircuitry that Prevents Hypoglycemia. Cell Metabolism, 5(5), 383-393. https://doi.org/10.1016/j.cmet.2007.04.001