A Parabrachial-Hypothalamic Cholecystokinin Neurocircuit Controls Counterregulatory Responses to Hypoglycemia

Alastair S Garfield, Bhavik P Shah, Joseph C Madara, Luke K Burke, Christa M Patterson, Jonathan Flak, Rachael L Neve, Mark L Evans, Bradford B Lowell, Martin G Myers, Lora K Heisler

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112 Citations (Scopus)
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Hypoglycemia engenders an autonomically mediated counterregulatory (CR)-response that stimulates endogenous glucose production to maintain concentrations within an appropriate physiological range. Although the involvement of the brain in preserving normoglycemia has been established, the neurocircuitry underlying centrally mediated CR-responses remains unclear. Here we demonstrate that lateral parabrachial nucleus cholecystokinin (CCK(LPBN)) neurons are a population of glucose-sensing cells (glucose inhibited) with counterregulatory capacity. Furthermore, we reveal that steroidogenic-factor 1 (SF1)-expressing neurons of the ventromedial nucleus of the hypothalamus (SF1(VMH)) are the specific target of CCK(LPBN) glucoregulatory neurons. This discrete CCK(LPBN)→SF1(VMH) neurocircuit is both necessary and sufficient for the induction of CR-responses. Together, these data identify CCK(LPBN) neurons, and specifically CCK neuropeptide, as glucoregulatory and provide significant insight into the homeostatic mechanisms controlling CR-responses to hypoglycemia.

Original languageEnglish
Pages (from-to)1030-1037
Number of pages8
JournalCell Metabolism
Issue number6
Publication statusPublished - 2 Dec 2014

Bibliographical note

This work was supported by the University of Edinburgh Chancellor’s Fellowship (A.S.G.), Wellcome Trust (L.K.H.; WT098012), and National Institutes of Health (B.B.L.; R01 DK096010, R01 DK089044, R01 DK071051, R01 DK075632, and R37 DK053477) (M.G.M.: R01 DK098853). Catecholamine assays were performed by the VUMC Hormone Assay Core (NIH grants DK059637 and DK020593).


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