CNS control of the endocrine pancreas
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REVIEW
CNS control of the endocrine pancreas Chelsea L. Faber 1,2
&
Jennifer D. Deem 1,2
&
Carlos A. Campos 1,2 & Gerald J. Taborsky Jr. 2,3 & Gregory J. Morton 1,2
Received: 3 March 2020 / Accepted: 7 May 2020 / Published online: 31 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Increasing evidence suggests that, although pancreatic islets can function autonomously to detect and respond to changes in the circulating glucose level, the brain cooperates with the islet to maintain glycaemic control. Here, we review the role of the central and autonomic nervous systems in the control of the endocrine pancreas, including mechanisms whereby the brain senses circulating blood glucose levels. We also examine whether dysfunction in these systems might contribute to complications of type 1 diabetes and the pathogenesis of type 2 diabetes. Keywords Autonomic nervous system . Brain . Diabetes . Glucagon . Glucose . Insulin . Islet . Pancreas . Review
Abbreviations ANS Autonomic nervous system ARC Arcuate nucleus BBB Blood–brain barrier CNS Central nervous system CRR Counter-regulatory responses CVO Circumventricular organs DMNX Dorsal motor nucleus of the vagus FGF Fibroblast growth factor GCK Glucokinase GSIS Glucose-stimulated insulin secretion GSN Glucose-sensing neuron HAAF Hypoglycaemia-associated autonomic failure i.c.v. Intracerebroventricular IIH Insulin-induced hypoglycaemia IML Interomediolateral ISF Interstitial fluid Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-020-05204-6) contains a slideset of the figures for download, which is available to authorised users. * Gregory J. Morton [email protected] 1
UW Medicine Diabetes Institute, Department of Medicine, University of Washington, 750 Republican St, Box 358062, Seattle, WA 98109, USA
2
Department of Medicine, University of Washington, Seattle, WA, USA
3
Veterans Affairs Puget Sound Health Care System, Department of Veterans Affairs Medical Center, Seattle, WA, USA
ME NTS PMV PNS POA SNS VMN
Median eminence Nucleus of the solitary tract Portal-mesenteric vein Parasympathetic nervous system Preoptic area Sympathetic nervous system Ventromedial nucleus
Introduction Blood glucose levels are maintained within narrow physiological limits. Whenever glucose levels deviate from their defended level, adaptive metabolic responses are engaged to ensure glucose levels return to the normal range. Critical to these responses are the capacities of pancreatic islet alpha and beta cells to coordinately adjust glucagon and insulin secretion, respectively, in response to changes in blood glucose concentrations. However, accumulating evidence suggests that the central nervous system (CNS) works in tandem with the islet to maintain glucose homeostasis [1]. Here, we review key evidence suggesting that: (1) the brain can regulate islet function directly via innervation by parasympathetic nervous system (PNS) and sympathetic nervous system (SNS) branches of the autonomic nervous system (
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