Zhao Wenjun, Li Aiyun, Feng Xin, Hou Ting, Liu Kang, Liu Baolin, Zhang Ning
Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 211198, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicines, Nanjing 211198, China.
Cell Signal. 2016 Sep;28(9):1401-1411. doi: 10.1016/j.cellsig.2016.06.018. Epub 2016 Jun 22.
This study aims to investigate the effects of metformin and resveratrol on muscle insulin resistance with emphasis on the regulation of lipolysis in hypoxic adipose tissue. ICR mice were fed with high fat diet (HFD) for 10days with administration of metformin, resveratrol, or intraperitoneal injection of digoxin. Adipose hypoxia, inflammation and cAMP/PKA-dependent lipolysis were investigated. Moreover, lipid deposition and insulin resistance were examined in the muscle. Metformin and resveratrol attenuated adipose hypoxia, inhibited HIF-1α expression and inflammation in the adipose tissue of HFD-fed mice. Metformin and resveratrol inhibited lipolysis through prevention of PKA/HSL activation by decreasing the accumulation of cAMP via preserving PDE3B. Metformin and resveratrol reduced FFAs influx and DAG accumulation, and thus improved insulin signaling in the muscle by inhibiting PKCθ translocation. This study presents a new view of regulating lipid metabolism to ameliorate insulin resistance and provides the clinical guiding significance for obesity and type 2 diabetes with metformin and resveratrol treatment.
本研究旨在探讨二甲双胍和白藜芦醇对肌肉胰岛素抵抗的影响，重点关注低氧脂肪组织中脂解作用的调节。将ICR小鼠用高脂饮食（HFD）喂养10天，并给予二甲双胍、白藜芦醇或腹腔注射地高辛。研究脂肪组织的低氧、炎症和cAMP/PKA依赖性脂解作用。此外，检测肌肉中的脂质沉积和胰岛素抵抗。二甲双胍和白藜芦醇减轻了脂肪组织低氧，抑制了HFD喂养小鼠脂肪组织中HIF-1α的表达和炎症。二甲双胍和白藜芦醇通过维持PDE3B来减少cAMP的积累，从而防止PKA/HSL激活，进而抑制脂解作用。二甲双胍和白藜芦醇减少了游离脂肪酸（FFAs）内流和二酰甘油（DAG）积累，从而通过抑制蛋白激酶Cθ（PKCθ）易位改善肌肉中的胰岛素信号。本研究提出了调节脂质代谢以改善胰岛素抵抗的新观点，并为二甲双胍和白藜芦醇治疗肥胖症和2型糖尿病提供了临床指导意义。
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