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

A distinct hypothalamus-to-β cell circuit modulates insulin secretion

  • Cell Metab. 2022 Feb 1;34(2):285-298.e7. doi: 10.1016/j.cmet.2021.12.020.
Ioannis Papazoglou 1 Ji-Hyeon Lee 2 Zhenzhong Cui 2 Chia Li 2 Gianluca Fulgenzi 3 Young Jae Bahn 2 Halina M Staniszewska-Goraczniak 4 Ramón A Piñol 2 Ian B Hogue 5 Lynn W Enquist 4 Michael J Krashes 2 Sushil G Rane 6
Affiliations

Affiliations

  • 1 Diabetes, Endocrinology and Obesity Branch, NIDDK, NIH, Bethesda, MD, USA. Electronic address: [email protected].
  • 2 Diabetes, Endocrinology and Obesity Branch, NIDDK, NIH, Bethesda, MD, USA.
  • 3 Neural Development Section, MCGP, CCR, NCI, NIH, Frederick, MD, USA; Department of Molecular and Clinical Sciences, Marche Polytechnic University, Ancona, Italy.
  • 4 Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
  • 5 Center for Immunotherapy, Vaccines, and Virotherapy, Biodesign Institute, School of Life Sciences, Arizona State University, Tempe, AZ, USA.
  • 6 Diabetes, Endocrinology and Obesity Branch, NIDDK, NIH, Bethesda, MD, USA. Electronic address: [email protected].
Abstract

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 β cells remain undefined. Here, we describe a functional transneuronal circuit connecting the hypothalamus to β cells in mice. This circuit originates from a subpopulation of oxytocin neurons in the paraventricular hypothalamic nucleus (PVNOXT), and it reaches the islets of the endocrine pancreas via the sympathetic autonomic branch to innervate β cells. Stimulation of PVNOXT neurons rapidly suppresses Insulin secretion and causes hyperglycemia. Conversely, silencing of these neurons elevates Insulin levels by dysregulating Neuronal Signaling and secretory pathways in β cells and induces hypoglycemia. PVNOXT neuronal activity is triggered by glucoprivation. Our findings reveal that a subset of PVNOXT neurons form functional multisynaptic circuits with β cells in mice to regulate Insulin secretion, and their function is necessary for the β cell response to hypoglycemia.

Keywords

central nervous system; glucoprivation; hypoglycemia; insulin secretion; oxytocin neurons; pancreatic β cells; paraventricular hypothalamic nucleus; pseudorabies tracing; sympathetic innervation; transneuronal circuit.

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