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Publication : A distinct hypothalamus-to-β cell circuit modulates insulin secretion.

First Author  Papazoglou I Year  2022
Journal  Cell Metab Volume  34
Issue  2 Pages  285-298.e7
PubMed ID  35108515 Mgi Jnum  J:343932
Mgi Id  MGI:6875527 Doi  10.1016/j.cmet.2021.12.020
Citation  Papazoglou I, et al. (2022) A distinct hypothalamus-to-beta cell circuit modulates insulin secretion. Cell Metab 34(2):285-298.e7
abstractText  The central nervous system has long been thought to regulate insulin secretion, an essential process in the maintenance of blood glucose levels. However, the anatomical and functional connections between the brain and insulin-producing pancreatic beta cells remain undefined. Here, we describe a functional transneuronal circuit connecting the hypothalamus to beta cells in mice. This circuit originates from a subpopulation of oxytocin neurons in the paraventricular hypothalamic nucleus (PVN(OXT)), and it reaches the islets of the endocrine pancreas via the sympathetic autonomic branch to innervate beta cells. Stimulation of PVN(OXT) neurons rapidly suppresses insulin secretion and causes hyperglycemia. Conversely, silencing of these neurons elevates insulin levels by dysregulating neuronal signaling and secretory pathways in beta cells and induces hypoglycemia. PVN(OXT) neuronal activity is triggered by glucoprivation. Our findings reveal that a subset of PVN(OXT) neurons form functional multisynaptic circuits with beta cells in mice to regulate insulin secretion, and their function is necessary for the beta cell response to hypoglycemia.
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