Insulin sensitizing effects of oligomannuronate-chromium (III) complexes in C2C12 skeletal muscle cells.
Insulin sensitizing effects of oligomannuronate-chromium (III) complexes in C2C12 skeletal muscle cells.
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低聚甘露糖醛酸铬 (III) 复合物对 C2C12 骨骼肌细胞的胰岛素增敏作用
DOI：
10.1371/journal.pone.0024598
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Yu G
中科院分区：
文献类型：
--
作者：
Hao C;Hao J;Wang W;Han Z;Li G;Zhang L;Zhao X;Yu G
背景众所周知，骨骼肌中的胰岛素抵抗是糖尿病的主要致病因素。因此，预防胰岛素抵抗引起的代谢紊乱、改善胰岛素敏感性对于2型糖尿病的治疗非常重要。在本研究中，我们研究了来自褐藻的海洋低聚糖寡甘露糖醛酸及其铬 (III) 复合物增强 C2C12 骨骼肌细胞胰岛素敏感性的能力。方法/主要发现 我们证明，低聚甘露糖醛酸，尤其是其铬 (III) 复合物，可增强胰岛素刺激的葡萄糖摄取，并在内化至 C2C12 骨骼肌细胞后增加葡萄糖转运蛋白 4 (GLUT4) 和胰岛素受体 (IR) 的 mRNA 表达。此外，寡糖处理还显着增强了 C2C12 细胞中 AMP 激活蛋白激酶 (AMPK)/乙酰辅酶 A 羧化酶 (ACC) 和磷酸肌醇 3-激酶 (PI3K)/蛋白激酶 B (Akt) 信号通路相关蛋白的磷酸化，表明寡糖同时激活胰岛素信号通路和 AMPK 通路作为其作用模式。此外，寡糖内化到C2C12细胞后分布到线粒体，并增加转录调节因子过氧化物酶体增殖物激活受体γ辅激活剂-1α（PGC-1α）、肉碱棕榈酰转移酶-1（CPT-1）和磷酸化乙酰辅酶A羧化酶（p-ACC）的表达，这表明这些寡糖的作用可能通过增加能量消耗与线粒体相关。海洋寡糖的所有这些作用与现有的抗糖尿病药物二甲双胍的作用相当。此外，寡糖治疗的毒性低于二甲双胍。结论/意义我们的研究结果表明，低聚甘露酸及其铬（III）复合物可改善C2C12骨骼肌细胞的胰岛素敏感性，并可作为一种低毒性的新型葡萄糖摄取刺激剂，可用作2型糖尿病的膳食补充剂或潜在药物。
Background 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. Methodology/Principal Findings 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. Conclusions/Significance 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.
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影响因子：
158.5
作者：
Cline, GW;Petersen, KF;Shulman, GI
通讯作者：
Shulman, GI
影响因子：
3.5
作者：
Kawada, A;Hiura, N;Takahara, H
通讯作者：
Takahara, H
影响因子：
3.1
作者：
NATSUME, M;KAMO, Y;ADACHI, T
通讯作者：
ADACHI, T
影响因子：
3.7
作者：
Jensen TE;Schjerling P;Viollet B;Wojtaszewski JF;Richter EA
通讯作者：
Richter EA
影响因子：
3.7
作者：
Ma, Jingui;Xin, Xianliang;Meng, Linghua;Tong, Linjiang;Lin, Liping;Geng, Meiyu;Ding, Jian
通讯作者：
Ding, Jian