Fu Wen-Cheng, Li Hai-Yan, Li Tian-Tian, Yang Kuo, Chen Jia-Xiang, Wang Si-Jia, Liu Chun-Hui, Zhang Wen
School of Life Sciences, East China Normal University, Shanghai, China.
China National Institute of Standardization, Beijing, China.
Food Nutr Res. 2021 Jan 22;65. doi: 10.29219/fnr.v65.4527. eCollection 2021.
Saturated fatty acids (SFAs) generally have been thought to worsen insulin-resistance and increase the risk of developing type 2 diabetes mellitus (T2DM). Recently, accumulating evidence has revealed that SFAs are not a single homogeneous group, instead different SFAs are associated with T2DM in opposing directions. Pentadecanoic acid (C15:0, PA) is directly correlated with dairy products, and a negative association between circulating PA and metabolic disease risk was observed in epidemiological studies. Therefore, the role of PA in human health needs to be reinforced. Whether PA has a direct benefit on glucose metabolism and insulin sensitivity needs further investigation.
The present study aimed to investigate the effect and potential mechanism of action of PA on basal and insulin stimulated glucose uptake in C2C12 myotubes.
Glucose uptake was determined using a 2-(N-[7-nitrobenz-2-oxa-1,3-diazol-4-yl] amino)-2-deoxyglucose (2-NBDG) uptake assay. Cell membrane proteins were isolated and glucose transporter 4 (GLUT4) protein was detected by western blotting to examine the translocation of GLUT4 to the plasma membrane. The phosphorylation levels of proteins involved in the insulin and 5'-adenosine monophosphate-activated protein kinase (AMPK) pathways were examined by western blotting.
We found that PA significantly promoted glucose uptake and GLUT4 translocation to the plasma membrane. PA had no effect on the insulin-dependent pathway involving insulin receptor substrate 1 (Tyr632) and protein kinase B (PKB/Akt), but increased phosphorylation of AMPK and Akt substrate of 160 kDa (AS160). Compound C (an AMPK inhibitor) blocked PA-induced AMPK activation and reversed PA-induced GLUT4 translocation, indicating that PA promotes glucose uptake via the AMPK pathway . Moreover, PA significantly promoted insulin-stimulated glucose uptake in myotubes. Under insulin stimulation, PA did not affect the insulin-dependent pathway, but still activated AMPK.
PA, an odd-chain SFA, significantly stimulates glucose uptake via the AMPK-AS160 pathway and exhibits an insulin-sensitizing effect in myotubes.
饱和脂肪酸（SFAs）通常被认为会加重胰岛素抵抗并增加患2型糖尿病（T2DM）的风险。最近，越来越多的证据表明，饱和脂肪酸并非单一的同质群体，相反，不同的饱和脂肪酸与2型糖尿病的关联方向相反。十五烷酸（C15:0，PA）与乳制品直接相关，并且在流行病学研究中观察到循环PA与代谢疾病风险之间存在负相关。因此，PA对人类健康的作用需要进一步加强。PA对葡萄糖代谢和胰岛素敏感性是否有直接益处需要进一步研究。
本研究旨在探讨PA对C2C12肌管基础和胰岛素刺激的葡萄糖摄取的影响及其潜在作用机制。
使用2-(N-[7-硝基苯并-2-恶唑-1,3-二氮杂环丁烷-4-基]氨基)-2-脱氧葡萄糖（2-NBDG）摄取试验测定葡萄糖摄取。分离细胞膜蛋白，通过蛋白质印迹法检测葡萄糖转运蛋白4（GLUT4）蛋白，以检查GLUT4向质膜的转位。通过蛋白质印迹法检测胰岛素和5'-腺苷单磷酸激活蛋白激酶（AMPK）途径中相关蛋白的磷酸化水平。
我们发现PA显著促进葡萄糖摄取和GLUT4向质膜的转位。PA对涉及胰岛素受体底物1（Tyr632）和蛋白激酶B（PKB/Akt）的胰岛素依赖性途径没有影响，但增加了AMPK和160 kDa的Akt底物（AS160）的磷酸化。化合物C（一种AMPK抑制剂）阻断了PA诱导的AMPK激活，并逆转了PA诱导的GLUT4转位，表明PA通过AMPK途径促进葡萄糖摄取。此外，PA显著促进肌管中胰岛素刺激的葡萄糖摄取。在胰岛素刺激下，PA不影响胰岛素依赖性途径，但仍激活AMPK。
PA，一种奇数链饱和脂肪酸，通过AMPK-AS160途径显著刺激葡萄糖摄取，并在肌管中表现出胰岛素增敏作用。
