A novel phenolic formulation for treating hepatic and peripheral insulin resistance by regulating GLUT4-mediated glucose uptake.
J Tradit Complement Med
; 12(2): 195-205, 2022 Mar.
Article
en En
| MEDLINE
| ID: mdl-35528476
ABSTRACT
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.
ACC, acetyl-CoA carboxylase; Abbreviations: 2DG, 2-deoxyglucose; BSA, bovine serum albumin; Bt2-cAMP, dibutyryl cAMP; CB, cytochalasin B; DAB, diaminobenzidine; DMEM, Dulbecco's modified Eagle's medium; DMSO, dimethyl sulfoxide; ECL, enhanced chemiluminescence; EGCG, epigallocatechin-3-O-gallate; Endosome; FBS, fetal bovine serum; FER, ferulic acid; GLUT4; GLUT4, glucose transporter-4; Glucose uptake; Hepatic glucose production; IDV, indinavir; IMCL, intramyocellular lipid; ISP, insulin signaling pathway; Insulin resistance; KHB, Krebs-Henseleit buffer; Metabolic syndrome; ORO, Oil Red O; PBS, phosphate-buffered saline; PVDF, polyvinylidene difluoride; Phenolic phytochemicals; RSV, resveratrol; SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis; T2DM, type 2 diabetes mellitus; Tf-HRP, Transferrin conjugated to horseradish peroxidase; Type 2 diabetes; α-MEM, α-minimal essential medium
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Bases de datos:
MEDLINE
Idioma:
En
Revista:
J Tradit Complement Med
Año:
2022
Tipo del documento:
Article
País de afiliación:
Taiwán