PACAP Neurons in the Ventromedial Hypothalamic Nucleus Are Glucose Inhibited and Their Selective Activation Induces Hyperglycaemia

Background: Glucose-sensing neurons are located in several parts of the brain, but are concentrated in the ventromedial nucleus of the hypothalamus (VMH). The importance of these VMH neurons in glucose homeostasis is well-established, however, little is known about their individual identity. In the...

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Main Authors: Tansi Khodai, Nicolas Nunn, Amy A. Worth, Claire H. Feetham, Mino D. C. Belle, Hugh D. Piggins, Simon M. Luckman
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-10-01
Series:Frontiers in Endocrinology
Subjects:
VMH
Online Access:https://www.frontiersin.org/article/10.3389/fendo.2018.00632/full
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spelling doaj-0b05d9e828ad4c47a2db06338b39acc62020-11-25T00:07:27ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922018-10-01910.3389/fendo.2018.00632415771PACAP Neurons in the Ventromedial Hypothalamic Nucleus Are Glucose Inhibited and Their Selective Activation Induces HyperglycaemiaTansi Khodai0Nicolas Nunn1Amy A. Worth2Claire H. Feetham3Mino D. C. Belle4Hugh D. Piggins5Simon M. Luckman6Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomMedical School, University of Exeter, Exeter, United KingdomFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomBackground: Glucose-sensing neurons are located in several parts of the brain, but are concentrated in the ventromedial nucleus of the hypothalamus (VMH). The importance of these VMH neurons in glucose homeostasis is well-established, however, little is known about their individual identity. In the present study, we identified a distinct glucose-sensing population in the VMH and explored its place in the glucose-regulatory network.Methods: Using patch-clamp electrophysiology on Pacap-cre::EYFP cells, we explored the glucose-sensing ability of the pituitary adenylate cyclase-activating peptide (PACAP) neurons both inside and outside the VMH. We also mapped the efferent projections of these neurons using anterograde and retrograde tracing techniques. Finally, to test the functionality of PACAPVMHin vivo, we used DREADD technology and measured systemic responses.Results: We demonstrate that PACAP neurons inside (PACAPVMH), but not outside the VMH are intrinsically glucose inhibited (GI). Anatomical tracing techniques show that PACAPVMH neurons project to several areas that can influence autonomic output. In vivo, chemogenetic stimulation of these neurons inhibits insulin secretion leading to reduced glucose tolerance, implicating their role in systemic glucose regulation.Conclusion: These findings are important as they identify, for the first time, a specific VMH neuronal population involved in glucose homeostasis. Identifying the different glucose-sensing populations in the VMH will help piece together the different arms of glucose regulation providing vital information regarding central responses to glucose metabolic disorders including hypoglycaemia.https://www.frontiersin.org/article/10.3389/fendo.2018.00632/fullPACAPVMHglucose sensingglucose inhibitedhypoglycaemia
collection DOAJ
language English
format Article
sources DOAJ
author Tansi Khodai
Nicolas Nunn
Amy A. Worth
Claire H. Feetham
Mino D. C. Belle
Hugh D. Piggins
Simon M. Luckman
spellingShingle Tansi Khodai
Nicolas Nunn
Amy A. Worth
Claire H. Feetham
Mino D. C. Belle
Hugh D. Piggins
Simon M. Luckman
PACAP Neurons in the Ventromedial Hypothalamic Nucleus Are Glucose Inhibited and Their Selective Activation Induces Hyperglycaemia
Frontiers in Endocrinology
PACAP
VMH
glucose sensing
glucose inhibited
hypoglycaemia
author_facet Tansi Khodai
Nicolas Nunn
Amy A. Worth
Claire H. Feetham
Mino D. C. Belle
Hugh D. Piggins
Simon M. Luckman
author_sort Tansi Khodai
title PACAP Neurons in the Ventromedial Hypothalamic Nucleus Are Glucose Inhibited and Their Selective Activation Induces Hyperglycaemia
title_short PACAP Neurons in the Ventromedial Hypothalamic Nucleus Are Glucose Inhibited and Their Selective Activation Induces Hyperglycaemia
title_full PACAP Neurons in the Ventromedial Hypothalamic Nucleus Are Glucose Inhibited and Their Selective Activation Induces Hyperglycaemia
title_fullStr PACAP Neurons in the Ventromedial Hypothalamic Nucleus Are Glucose Inhibited and Their Selective Activation Induces Hyperglycaemia
title_full_unstemmed PACAP Neurons in the Ventromedial Hypothalamic Nucleus Are Glucose Inhibited and Their Selective Activation Induces Hyperglycaemia
title_sort pacap neurons in the ventromedial hypothalamic nucleus are glucose inhibited and their selective activation induces hyperglycaemia
publisher Frontiers Media S.A.
series Frontiers in Endocrinology
issn 1664-2392
publishDate 2018-10-01
description Background: Glucose-sensing neurons are located in several parts of the brain, but are concentrated in the ventromedial nucleus of the hypothalamus (VMH). The importance of these VMH neurons in glucose homeostasis is well-established, however, little is known about their individual identity. In the present study, we identified a distinct glucose-sensing population in the VMH and explored its place in the glucose-regulatory network.Methods: Using patch-clamp electrophysiology on Pacap-cre::EYFP cells, we explored the glucose-sensing ability of the pituitary adenylate cyclase-activating peptide (PACAP) neurons both inside and outside the VMH. We also mapped the efferent projections of these neurons using anterograde and retrograde tracing techniques. Finally, to test the functionality of PACAPVMHin vivo, we used DREADD technology and measured systemic responses.Results: We demonstrate that PACAP neurons inside (PACAPVMH), but not outside the VMH are intrinsically glucose inhibited (GI). Anatomical tracing techniques show that PACAPVMH neurons project to several areas that can influence autonomic output. In vivo, chemogenetic stimulation of these neurons inhibits insulin secretion leading to reduced glucose tolerance, implicating their role in systemic glucose regulation.Conclusion: These findings are important as they identify, for the first time, a specific VMH neuronal population involved in glucose homeostasis. Identifying the different glucose-sensing populations in the VMH will help piece together the different arms of glucose regulation providing vital information regarding central responses to glucose metabolic disorders including hypoglycaemia.
topic PACAP
VMH
glucose sensing
glucose inhibited
hypoglycaemia
url https://www.frontiersin.org/article/10.3389/fendo.2018.00632/full
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