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Extracellular Signal–Regulated Kinase in the Ventromedial Hypothalamus Mediates Leptin-Induced Glucose Uptake in Red-Type Skeletal Muscle
Leptin is a key regulator of glucose metabolism in mammals, but the mechanisms of its action have remained elusive. We now show that signaling by extracellular signal–regulated kinase (ERK) and its upstream kinase MEK in the ventromedial hypothalamus (VMH) mediates the leptin-induced increase in glu...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712028/ https://www.ncbi.nlm.nih.gov/pubmed/23530005 http://dx.doi.org/10.2337/db12-1629 |
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author | Toda, Chitoku Shiuchi, Tetsuya Kageyama, Haruaki Okamoto, Shiki Coutinho, Eulalia A. Sato, Tatsuya Okamatsu-Ogura, Yuko Yokota, Shigefumi Takagi, Kazuyo Tang, Lijun Saito, Kumiko Shioda, Seiji Minokoshi, Yasuhiko |
author_facet | Toda, Chitoku Shiuchi, Tetsuya Kageyama, Haruaki Okamoto, Shiki Coutinho, Eulalia A. Sato, Tatsuya Okamatsu-Ogura, Yuko Yokota, Shigefumi Takagi, Kazuyo Tang, Lijun Saito, Kumiko Shioda, Seiji Minokoshi, Yasuhiko |
author_sort | Toda, Chitoku |
collection | PubMed |
description | Leptin is a key regulator of glucose metabolism in mammals, but the mechanisms of its action have remained elusive. We now show that signaling by extracellular signal–regulated kinase (ERK) and its upstream kinase MEK in the ventromedial hypothalamus (VMH) mediates the leptin-induced increase in glucose utilization as well as its insulin sensitivity in the whole body and in red-type skeletal muscle of mice through activation of the melanocortin receptor (MCR) in the VMH. In contrast, activation of signal transducer and activator of transcription 3 (STAT3), but not the MEK-ERK pathway, in the VMH by leptin enhances the insulin-induced suppression of endogenous glucose production in an MCR-independent manner, with this effect of leptin occurring only in the presence of an increased plasma concentration of insulin. Given that leptin requires 6 h to increase muscle glucose uptake, the transient activation of the MEK-ERK pathway in the VMH by leptin may play a role in the induction of synaptic plasticity in the VMH, resulting in the enhancement of MCR signaling in the nucleus and leading to an increase in insulin sensitivity in red-type muscle. |
format | Online Article Text |
id | pubmed-3712028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-37120282014-07-01 Extracellular Signal–Regulated Kinase in the Ventromedial Hypothalamus Mediates Leptin-Induced Glucose Uptake in Red-Type Skeletal Muscle Toda, Chitoku Shiuchi, Tetsuya Kageyama, Haruaki Okamoto, Shiki Coutinho, Eulalia A. Sato, Tatsuya Okamatsu-Ogura, Yuko Yokota, Shigefumi Takagi, Kazuyo Tang, Lijun Saito, Kumiko Shioda, Seiji Minokoshi, Yasuhiko Diabetes Original Research Leptin is a key regulator of glucose metabolism in mammals, but the mechanisms of its action have remained elusive. We now show that signaling by extracellular signal–regulated kinase (ERK) and its upstream kinase MEK in the ventromedial hypothalamus (VMH) mediates the leptin-induced increase in glucose utilization as well as its insulin sensitivity in the whole body and in red-type skeletal muscle of mice through activation of the melanocortin receptor (MCR) in the VMH. In contrast, activation of signal transducer and activator of transcription 3 (STAT3), but not the MEK-ERK pathway, in the VMH by leptin enhances the insulin-induced suppression of endogenous glucose production in an MCR-independent manner, with this effect of leptin occurring only in the presence of an increased plasma concentration of insulin. Given that leptin requires 6 h to increase muscle glucose uptake, the transient activation of the MEK-ERK pathway in the VMH by leptin may play a role in the induction of synaptic plasticity in the VMH, resulting in the enhancement of MCR signaling in the nucleus and leading to an increase in insulin sensitivity in red-type muscle. American Diabetes Association 2013-07 2013-06-14 /pmc/articles/PMC3712028/ /pubmed/23530005 http://dx.doi.org/10.2337/db12-1629 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Original Research Toda, Chitoku Shiuchi, Tetsuya Kageyama, Haruaki Okamoto, Shiki Coutinho, Eulalia A. Sato, Tatsuya Okamatsu-Ogura, Yuko Yokota, Shigefumi Takagi, Kazuyo Tang, Lijun Saito, Kumiko Shioda, Seiji Minokoshi, Yasuhiko Extracellular Signal–Regulated Kinase in the Ventromedial Hypothalamus Mediates Leptin-Induced Glucose Uptake in Red-Type Skeletal Muscle |
title | Extracellular Signal–Regulated Kinase in the Ventromedial Hypothalamus Mediates Leptin-Induced Glucose Uptake in Red-Type Skeletal Muscle |
title_full | Extracellular Signal–Regulated Kinase in the Ventromedial Hypothalamus Mediates Leptin-Induced Glucose Uptake in Red-Type Skeletal Muscle |
title_fullStr | Extracellular Signal–Regulated Kinase in the Ventromedial Hypothalamus Mediates Leptin-Induced Glucose Uptake in Red-Type Skeletal Muscle |
title_full_unstemmed | Extracellular Signal–Regulated Kinase in the Ventromedial Hypothalamus Mediates Leptin-Induced Glucose Uptake in Red-Type Skeletal Muscle |
title_short | Extracellular Signal–Regulated Kinase in the Ventromedial Hypothalamus Mediates Leptin-Induced Glucose Uptake in Red-Type Skeletal Muscle |
title_sort | extracellular signal–regulated kinase in the ventromedial hypothalamus mediates leptin-induced glucose uptake in red-type skeletal muscle |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712028/ https://www.ncbi.nlm.nih.gov/pubmed/23530005 http://dx.doi.org/10.2337/db12-1629 |
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