[PDF][PDF] A parabrachial-hypothalamic cholecystokinin neurocircuit controls counterregulatory responses to hypoglycemia

AS Garfield, BP Shah, JC Madara, LK Burke… - Cell metabolism, 2014 - cell.com
AS Garfield, BP Shah, JC Madara, LK Burke, CM Patterson, J Flak, RL Neve, ML Evans
Cell metabolism, 2014cell.com
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 …
Summary
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 (CCKLPBN) 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 (SF1VMH) are the specific target of CCKLPBN glucoregulatory neurons. This discrete CCKLPBN→SF1VMH neurocircuit is both necessary and sufficient for the induction of CR-responses. Together, these data identify CCKLPBN neurons, and specifically CCK neuropeptide, as glucoregulatory and provide significant insight into the homeostatic mechanisms controlling CR-responses to hypoglycemia.
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