Insulin sensitizing effects of oligomannuronate-chromium (III) complexes in C2C12 skeletal muscle cells.

<h4>Background</h4>It was known that the insulin resistance in skeletal muscle is a major pathogenic factor in diabetes mellitus. Therefore prevention of metabolic disorder caused by insulin resistance and improvement of insulin sensitivity are very important for the therapy of type 2 di...

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Autores principales: Cui Hao, Jiejie Hao, Wei Wang, Zhangrun Han, Guangsheng Li, Lijuan Zhang, Xia Zhao, Guangli Yu
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:d0b3f9bac6074951bedbf82232e7c19d2021-11-04T06:08:31ZInsulin sensitizing effects of oligomannuronate-chromium (III) complexes in C2C12 skeletal muscle cells.1932-620310.1371/journal.pone.0024598https://doaj.org/article/d0b3f9bac6074951bedbf82232e7c19d2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21935427/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>It was known that the insulin resistance in skeletal muscle is a major pathogenic factor in diabetes mellitus. Therefore prevention of metabolic disorder caused by insulin resistance and improvement of insulin sensitivity are very important for the therapy of type 2 diabetes. In the present study, we investigated the ability of marine oligosaccharides oligomannuronate and its chromium (III) complexes from brown alga to enhance insulin sensitivity in C2C12 skeletal muscle cells.<h4>Methodology/principal findings</h4>We demonstrated that oligomannuronate, especially its chromium (III) complexes, enhanced insulin-stimulated glucose uptake and increased the mRNA expression of glucose transporter 4 (GLUT4) and insulin receptor (IR) after their internalization into C2C12 skeletal muscle cells. Additionally, oligosaccharides treatment also significantly enhanced the phosphorylation of proteins involved in both AMP activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathways in C2C12 cells, indicating that the oligosaccharides activated both the insulin signal pathway and AMPK pathways as their mode of action. Moreover, oligosaccharides distributed to the mitochondria after internalization into C2C12 cells and increased the expression of transcriptional regulator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), carnitine palmitoyl transferase-1 (CPT-1), and phosphorylated acetyl-CoA carboxylase (p-ACC), which suggested that the actions of these oligosaccharides might be associated with mitochondria through increasing energy expenditure. All of these effects of marine oligosaccharides were comparable to that of the established anti-diabetic drug, metformin. In addition, the treatment with oligosaccharides showed less toxicity than that of metformin.<h4>Conclusions/significance</h4>Our findings indicate that oligomannuonate and its chromium (III) complexes improved insulin sensitivity in C2C12 skeletal muscle cells, and acted as a novel glucose uptake stimulator with low toxicity, and could be used as dietary supplementary or potential drug for type 2 diabetes mellitus.Cui HaoJiejie HaoWei WangZhangrun HanGuangsheng LiLijuan ZhangXia ZhaoGuangli YuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e24598 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Cui Hao
Jiejie Hao
Wei Wang
Zhangrun Han
Guangsheng Li
Lijuan Zhang
Xia Zhao
Guangli Yu
Insulin sensitizing effects of oligomannuronate-chromium (III) complexes in C2C12 skeletal muscle cells.
description <h4>Background</h4>It was known that the insulin resistance in skeletal muscle is a major pathogenic factor in diabetes mellitus. Therefore prevention of metabolic disorder caused by insulin resistance and improvement of insulin sensitivity are very important for the therapy of type 2 diabetes. In the present study, we investigated the ability of marine oligosaccharides oligomannuronate and its chromium (III) complexes from brown alga to enhance insulin sensitivity in C2C12 skeletal muscle cells.<h4>Methodology/principal findings</h4>We demonstrated that oligomannuronate, especially its chromium (III) complexes, enhanced insulin-stimulated glucose uptake and increased the mRNA expression of glucose transporter 4 (GLUT4) and insulin receptor (IR) after their internalization into C2C12 skeletal muscle cells. Additionally, oligosaccharides treatment also significantly enhanced the phosphorylation of proteins involved in both AMP activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathways in C2C12 cells, indicating that the oligosaccharides activated both the insulin signal pathway and AMPK pathways as their mode of action. Moreover, oligosaccharides distributed to the mitochondria after internalization into C2C12 cells and increased the expression of transcriptional regulator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), carnitine palmitoyl transferase-1 (CPT-1), and phosphorylated acetyl-CoA carboxylase (p-ACC), which suggested that the actions of these oligosaccharides might be associated with mitochondria through increasing energy expenditure. All of these effects of marine oligosaccharides were comparable to that of the established anti-diabetic drug, metformin. In addition, the treatment with oligosaccharides showed less toxicity than that of metformin.<h4>Conclusions/significance</h4>Our findings indicate that oligomannuonate and its chromium (III) complexes improved insulin sensitivity in C2C12 skeletal muscle cells, and acted as a novel glucose uptake stimulator with low toxicity, and could be used as dietary supplementary or potential drug for type 2 diabetes mellitus.
format article
author Cui Hao
Jiejie Hao
Wei Wang
Zhangrun Han
Guangsheng Li
Lijuan Zhang
Xia Zhao
Guangli Yu
author_facet Cui Hao
Jiejie Hao
Wei Wang
Zhangrun Han
Guangsheng Li
Lijuan Zhang
Xia Zhao
Guangli Yu
author_sort Cui Hao
title Insulin sensitizing effects of oligomannuronate-chromium (III) complexes in C2C12 skeletal muscle cells.
title_short Insulin sensitizing effects of oligomannuronate-chromium (III) complexes in C2C12 skeletal muscle cells.
title_full Insulin sensitizing effects of oligomannuronate-chromium (III) complexes in C2C12 skeletal muscle cells.
title_fullStr Insulin sensitizing effects of oligomannuronate-chromium (III) complexes in C2C12 skeletal muscle cells.
title_full_unstemmed Insulin sensitizing effects of oligomannuronate-chromium (III) complexes in C2C12 skeletal muscle cells.
title_sort insulin sensitizing effects of oligomannuronate-chromium (iii) complexes in c2c12 skeletal muscle cells.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/d0b3f9bac6074951bedbf82232e7c19d
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