Natriuretic peptides promote glucose uptake in a cGMP-dependent manner in human adipocytes

Abstract Robust associations between low plasma level of natriuretic peptides (NP) and increased risk of type 2 diabetes (T2D) have been recently reported in humans. Adipose tissue (AT) is a known target of NP. However it is unknown whether NP signalling in human AT relates to insulin sensitivity an...

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Autores principales: Marine Coué, Valentin Barquissau, Pauline Morigny, Katie Louche, Corinne Lefort, Aline Mairal, Christian Carpéné, Nathalie Viguerie, Peter Arner, Dominique Langin, Mikael Rydén, Cedric Moro
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Publicado: Nature Portfolio 2018
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spelling oai:doaj.org-article:9d92cf21c52b4f298988c3800c26ac7e2021-12-02T15:05:30ZNatriuretic peptides promote glucose uptake in a cGMP-dependent manner in human adipocytes10.1038/s41598-018-19619-02045-2322https://doaj.org/article/9d92cf21c52b4f298988c3800c26ac7e2018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-19619-0https://doaj.org/toc/2045-2322Abstract Robust associations between low plasma level of natriuretic peptides (NP) and increased risk of type 2 diabetes (T2D) have been recently reported in humans. Adipose tissue (AT) is a known target of NP. However it is unknown whether NP signalling in human AT relates to insulin sensitivity and modulates glucose metabolism. We here show in two European cohorts that the NP receptor guanylyl cyclase-A (GC-A) expression in subcutaneous AT was down-regulated as a function of obesity grade while adipose NP clearance receptor (NPRC) was up-regulated. Adipose GC-A mRNA level was down-regulated in prediabetes and T2D, and negatively correlated with HOMA-IR and fasting blood glucose. We show for the first time that NP promote glucose uptake in a dose-dependent manner. This effect is reduced in adipocytes of obese individuals. NP activate mammalian target of rapamycin complex 1/2 (mTORC1/2) and Akt signalling. These effects were totally abrogated by inhibition of cGMP-dependent protein kinase and mTORC1/2 by rapamycin. We further show that NP treatment favoured glucose oxidation and de novo lipogenesis independently of significant gene regulation. Collectively, our data support a role for NP in blood glucose control and insulin sensitivity by increasing glucose uptake in human adipocytes. This effect is partly blunted in obesity.Marine CouéValentin BarquissauPauline MorignyKatie LoucheCorinne LefortAline MairalChristian CarpénéNathalie VigueriePeter ArnerDominique LanginMikael RydénCedric MoroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Marine Coué
Valentin Barquissau
Pauline Morigny
Katie Louche
Corinne Lefort
Aline Mairal
Christian Carpéné
Nathalie Viguerie
Peter Arner
Dominique Langin
Mikael Rydén
Cedric Moro
Natriuretic peptides promote glucose uptake in a cGMP-dependent manner in human adipocytes
description Abstract Robust associations between low plasma level of natriuretic peptides (NP) and increased risk of type 2 diabetes (T2D) have been recently reported in humans. Adipose tissue (AT) is a known target of NP. However it is unknown whether NP signalling in human AT relates to insulin sensitivity and modulates glucose metabolism. We here show in two European cohorts that the NP receptor guanylyl cyclase-A (GC-A) expression in subcutaneous AT was down-regulated as a function of obesity grade while adipose NP clearance receptor (NPRC) was up-regulated. Adipose GC-A mRNA level was down-regulated in prediabetes and T2D, and negatively correlated with HOMA-IR and fasting blood glucose. We show for the first time that NP promote glucose uptake in a dose-dependent manner. This effect is reduced in adipocytes of obese individuals. NP activate mammalian target of rapamycin complex 1/2 (mTORC1/2) and Akt signalling. These effects were totally abrogated by inhibition of cGMP-dependent protein kinase and mTORC1/2 by rapamycin. We further show that NP treatment favoured glucose oxidation and de novo lipogenesis independently of significant gene regulation. Collectively, our data support a role for NP in blood glucose control and insulin sensitivity by increasing glucose uptake in human adipocytes. This effect is partly blunted in obesity.
format article
author Marine Coué
Valentin Barquissau
Pauline Morigny
Katie Louche
Corinne Lefort
Aline Mairal
Christian Carpéné
Nathalie Viguerie
Peter Arner
Dominique Langin
Mikael Rydén
Cedric Moro
author_facet Marine Coué
Valentin Barquissau
Pauline Morigny
Katie Louche
Corinne Lefort
Aline Mairal
Christian Carpéné
Nathalie Viguerie
Peter Arner
Dominique Langin
Mikael Rydén
Cedric Moro
author_sort Marine Coué
title Natriuretic peptides promote glucose uptake in a cGMP-dependent manner in human adipocytes
title_short Natriuretic peptides promote glucose uptake in a cGMP-dependent manner in human adipocytes
title_full Natriuretic peptides promote glucose uptake in a cGMP-dependent manner in human adipocytes
title_fullStr Natriuretic peptides promote glucose uptake in a cGMP-dependent manner in human adipocytes
title_full_unstemmed Natriuretic peptides promote glucose uptake in a cGMP-dependent manner in human adipocytes
title_sort natriuretic peptides promote glucose uptake in a cgmp-dependent manner in human adipocytes
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/9d92cf21c52b4f298988c3800c26ac7e
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