A novel phenolic formulation for treating hepatic and peripheral insulin resistance by regulating GLUT4-mediated glucose uptake

Bean bu Kang ； Been huang Chiang

《Journal of Traditional and Complementary Medicine》 12卷2期 (2022/03) Pp. 195-205

https://doi.org/10.1016/j.jtcme.2021.08.004

摘要

Chronic insulin resistance suppresses muscle and liver response to insulin, which is partially due to impaired vesicle trafficking. We report here that a formula consisting of resveratrol, ferulic acid and epigallocatechin-3-O-gallate is more effective in ameliorating muscle and hepatic insulin resistance than the anti-diabetic drugs, metformin and AICAR. The formula enhanced glucose transporter-4 (GLUT4) translocation to the plasma membrane in the insulin-resistant muscle cells by regulating both insulin-independent (calcium and AMPK) and insulin-dependent (PI3K) signaling molecules. Particularly, it regulated the subcellular location of GLUT4 through endosomes to increase glucose uptake under insulin-resistant condition. Meanwhile, this phytochemicals combination increased glycogen synthesis and decreased glucose production in the insulin-resistant liver cells. On the other hand, this formula also showed anti-diabetic potential by the reduction of lipid content in the myotubes, hepatocytes, and adipocytes. This study demonstrated that the three phenolic compounds in the formula could work in distinct mechanisms and enhance both insulin-dependent and independent vesicles trafficking and glucose transport mechanisms to improve carbohydrate and lipid metabolism.

關鍵字

Phenolic phytochemicals ； Endosome ； GLUT4 ； Glucose uptake ； Hepatic glucose production ； Insulin resistance ； Metabolic syndrome ； Type 2 diabetes

參考文獻

Al Rashid MH, Majumder S, Mandal V, Mandal SC, Thandavarayan RA. In search of suitable extraction technique for large scale commercial production of bioactive fraction for the treatment of diabetes: the case Diospyros melanoxylon Roxb. J Tradit Complement Med. 2019;9:106-118. https://doi.org/10.1016/j.jtcme.2017.11.003

Xiao J, So KF, Liong EC, Tipoe GL. Recent advances in the herbal treatment of non-alcoholic fatty liver disease. J Tradit Complement Med. 2013;3:88-94. https://doi.org/10.4103/2225-4110.110411

Tadayon M, Movahedi S, Abedi P, Syahpoosh A. Impact of green tea extract on serum lipid of postmenopausal women: a randomized controlled trial. J Tradit Complement Med. 2018;8:391-395. https://doi.org/10.1016/j.jtcme.2017.07.005

Isidoro C. Nutraceuticals and diet in human health and disease. The special issue at a glance. J Tradit Complement Med. 2020;10:175-179. https://doi.org/10.1016/j.jtcme.2020.06.002

Haeusler RA, McGraw TE, Accili D. Biochemical and cellular properties of insulin receptor signalling. Nat Rev Mol Cell Biol. 2018;19:31-44. https://doi.org/10.1038/nrm.2017.89