@article{1ca06ff760604bc8ac9fb38ce63f666b,
title = "Synaptic Glutamate Release by Ventromedial Hypothalamic Neurons Is Part of the Neurocircuitry that Prevents Hypoglycemia",
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.",
keywords = "HUMDISEASE, MOLNEURO",
author = "Qingchun Tong and ChianPing Ye and McCrimmon, {Rory J.} and Harveen Dhillon and Brian Choi and Kramer, {Melissa D.} and Jia Yu and Zongfang Yang and Christiansen, {Lauryn M.} and Lee, {Charlotte E.} and Choi, {Cheol Soo} and Zigman, {Jeffrey M.} and Shulman, {Gerald I.} and Sherwin, {Robert S.} and Elmquist, {Joel K.} and Lowell, {Bradford B.}",
note = "Funding Information: The authors acknowledge B. Bean and J. Lu for helpful discussions. This work was supported by the National Institutes of Health (RO1 DK071051 and PO1 DK56116 to B.B.L., R01 DK072409 and R37 DK020495 to R.S.S., R01 DK069831 to R.J.M., and DK071320 to J.K.E.), the NIH-funded Boston Obesity Nutrition Research Center (P30 DK046200; the Transgenic Core, directed by B.B.L., helped generate the Sf1-Cre transgenic mice and the Vglut2 flox/flox mice, and H.D. was the recipient of a Pilot and Feasibility Award), the NIH-funded Boston Area Diabetes Endocrinology Research Center (P30 DK057521; the Transgenic Core, directed by B.B.L., helped generate mice as above), the NIH-funded Program Project Energy Expenditure Core (PO1 DK56116), the Smith Family Foundation Pinnacle Program Project Award from the American Diabetes Association (J.K.E.), the Juvenile Diabetes Research Foundation Center for the Study of Hypoglycemia (R.S.S.), and the American Heart Association (fellowships to Q.T. and H.D.). ",
year = "2007",
month = may,
day = "9",
doi = "10.1016/j.cmet.2007.04.001",
language = "English (US)",
volume = "5",
pages = "383--393",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "5",
}