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  • Glucose Uptake Is Increased by Estradiol Dipropionate in L6 Skeletal Muscle Cells.

Glucose Uptake Is Increased by Estradiol Dipropionate in L6 Skeletal Muscle Cells.

Pharmaceuticals (Basel, Switzerland) (2023-01-22)
Yanhong Yao, Xinzhou Yang, Jinhua Shen, Ping Zhao
ABSTRACT

GLUT4 is an important glucose transporter, which is closely related to insulin resistance and type 2 diabetes. In this study, we investigated the mechanism of Estradiol Dipropionate (EDP) on uptake of glucose in L6 skeletal muscle cells. In our study, we confirmed that EDP promoted uptake of glucose in L6 skeletal muscle cells in both normal and insulin resistant models. Western blot indicated that EDP accelerated GLUT4 expression and significantly activated AMPK and PKC phosphorylation; the expression of GLUT4 was significantly inhibited by AMPK inhibitor compound C and PKC inhibitor Gö6983, but not by Wortmannin (Akt inhibitor). Meanwhile, EDP boosted GLUT4 expression, and also increased intracellular Ca2+ levels. In the presence of 2 mM, 0 mM extracellular Ca2+ and 0 mM extracellular Ca2+ + BAPTA-AM, the involvement of intracellular Ca2+ levels contribute to EDP-induced GLUT4 expression and fusion with plasma membrane. Therefore, this study investigated whether EDP promoted GLUT4 expression through AMPK and PKC signaling pathways, thereby enhancing GLUT4 uptake of glucose and fusion into plasma membrane in L6 skeletal muscle cells. In addition, both EDP induced GLUT4 translocation and uptake of glucose were Ca2+ dependent. These findings suggested that EDP may be potential drug for the treatment of type 2 diabetes.

MATERIALS
Product Number
Brand
Product Description

Millipore
BAPTA/AM, Membrane-permeable form of BAPTA.
Sigma-Aldrich
Wortmannin, InSolution, ≥95%, fungal metabolite that acts as a selective, cell-permeable and irreversible inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase)