Hypothalamic sensing of circulating lactate regulates glucose production

Emerging studies indicate that hypothalamic hormonal signalling pathways and nutrient metabolism regulate glucose homeostasis in rodents. Although hypothalamic lactate-sensing mechanisms have been described to lower glucose production (GP), it is currently unknown whether the hypothalamus senses lac...

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Main Authors:	Kokorovic, Andrea, Cheung, Grace WC, Rossetti, Luciano, Lam, Tony KT
Format:	Online
Language:	English
Published:	John Wiley & Sons, Ltd 2009
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515055/

id	pubmed-4515055
recordtype	oai_dc
spelling	pubmed-45150552015-07-27 Hypothalamic sensing of circulating lactate regulates glucose production Kokorovic, Andrea Cheung, Grace WC Rossetti, Luciano Lam, Tony KT Short Communications Emerging studies indicate that hypothalamic hormonal signalling pathways and nutrient metabolism regulate glucose homeostasis in rodents. Although hypothalamic lactate-sensing mechanisms have been described to lower glucose production (GP), it is currently unknown whether the hypothalamus senses lactate in the blood circulation to regulate GP and maintain glucose homeostasis in vivo. To examine whether hypothalamic sensing of circulating lactate is required to regulate GP, we infused intravenous (i.v.) lactate in the absence or presence of inhibition of central/hypothalamic lactate-sensing mechanisms in normal rodents. Inhibition of central/hypothalamic lactate-sensing mechanisms was achieved by three independent approaches. Tracer-dilution methodology in combination with the pancreatic clamp technique was used to assess the effect of i.v. and central/hypothalamic administrations on glucose metabolism in vivo. In the presence of physiologically relevant increases in the levels of plasma lactate, inhibition of central lactate-sensing mechanisms by lactate dehydrogenase inhibitor oxamate (OXA) or ATP-sensitive potassium channels blocker glibenclamide increased GP. Furthermore, direct administration of OXA into the mediobasal hypothalamus increased GP in the presence of similar elevation of circulating lactate. Together, these data indicate that hypothalamic sensing of circulating lactate regulates GP and is required to maintain glucose homeostasis. John Wiley & Sons, Ltd 2009 2008-11-18 /pmc/articles/PMC4515055/ /pubmed/19040414 http://dx.doi.org/10.1111/j.1582-4934.2008.00596.x Text en © 2008 The Authors Journal compilation © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kokorovic, Andrea Cheung, Grace WC Rossetti, Luciano Lam, Tony KT
spellingShingle	Kokorovic, Andrea Cheung, Grace WC Rossetti, Luciano Lam, Tony KT Hypothalamic sensing of circulating lactate regulates glucose production
author_facet	Kokorovic, Andrea Cheung, Grace WC Rossetti, Luciano Lam, Tony KT
author_sort	Kokorovic, Andrea
title	Hypothalamic sensing of circulating lactate regulates glucose production
title_short	Hypothalamic sensing of circulating lactate regulates glucose production
title_full	Hypothalamic sensing of circulating lactate regulates glucose production
title_fullStr	Hypothalamic sensing of circulating lactate regulates glucose production
title_full_unstemmed	Hypothalamic sensing of circulating lactate regulates glucose production
title_sort	hypothalamic sensing of circulating lactate regulates glucose production
description	Emerging studies indicate that hypothalamic hormonal signalling pathways and nutrient metabolism regulate glucose homeostasis in rodents. Although hypothalamic lactate-sensing mechanisms have been described to lower glucose production (GP), it is currently unknown whether the hypothalamus senses lactate in the blood circulation to regulate GP and maintain glucose homeostasis in vivo. To examine whether hypothalamic sensing of circulating lactate is required to regulate GP, we infused intravenous (i.v.) lactate in the absence or presence of inhibition of central/hypothalamic lactate-sensing mechanisms in normal rodents. Inhibition of central/hypothalamic lactate-sensing mechanisms was achieved by three independent approaches. Tracer-dilution methodology in combination with the pancreatic clamp technique was used to assess the effect of i.v. and central/hypothalamic administrations on glucose metabolism in vivo. In the presence of physiologically relevant increases in the levels of plasma lactate, inhibition of central lactate-sensing mechanisms by lactate dehydrogenase inhibitor oxamate (OXA) or ATP-sensitive potassium channels blocker glibenclamide increased GP. Furthermore, direct administration of OXA into the mediobasal hypothalamus increased GP in the presence of similar elevation of circulating lactate. Together, these data indicate that hypothalamic sensing of circulating lactate regulates GP and is required to maintain glucose homeostasis.
publisher	John Wiley & Sons, Ltd
publishDate	2009
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515055/
_version_	1613252200871493632

Hypothalamic sensing of circulating lactate regulates glucose production

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