A Parabrachial-Hypothalamic Cholecystokinin Neurocircuit Controls Counterregulatory Responses to Hypoglycemia

摘要: Hypoglycemia engenders an autonomically mediated counterregulatory (CR)-response that stimulates endogenous glucose production to maintain concentrations within appropriate physiological range. Although the involvement of brain in preserving normoglycemia has been established, neurocircuitry underlying centrally CR-responses remains unclear. Here we demonstrate lateral parabrachial nucleus cholecystokinin (CCKLPBN) neurons are a population glucose-sensing cells (glucose inhibited) with capacity. Furthermore, reveal steroidogenic-factor 1 (SF1)-expressing ventromedial hypothalamus (SF1VMH) specific target CCKLPBN glucoregulatory neurons. This discrete CCKLPBN→SF1VMH neurocircuit is both necessary and sufficient for induction CR-responses. Together, these data identify neurons, specifically CCK neuropeptide, as provide significant insight into homeostatic mechanisms controlling hypoglycemia.