Ethanolic Extract of Folium Sennae Mediates the Glucose Uptake of L6 Cells by GLUT4 and Ca2.

Jinhua Shen,Qian Ming,Di Tian,Xinzhou Yang,Qing-Hua Liu,Junying Qiu,Ping Zhao,Jia Liu

doi:10.3390/molecules23112934

Jinhua Shen, Qian Ming + Show 6 more

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https://doi.org/10.3390/molecules23112934

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Abstract

In today’s world, diabetes mellitus (DM) is on the rise, especially type 2 diabetes mellitus (T2DM), which is characterized by insulin resistance. T2DM has high morbidity, and therapies with natural products have attracted much attention in the recent past. In this paper, we aimed to study the hypoglycemic effect and the mechanism of an ethanolic extract of Folium Sennae (FSE) on L6 cells. The glucose uptake of L6 cells was investigated using a glucose assay kit. We studied glucose transporter 4 (GLUT4) expression and AMP-activated protein kinase (AMPK), protein kinase B (PKB/Akt), and protein kinase C (PKC) phosphorylation levels using western blot analysis. GLUT4 trafficking and intracellular Ca2+ levels were monitored by laser confocal microscopy in L6 cells stably expressing IRAP-mOrange. GLUT4 fusion with plasma membrane (PM) was observed by myc-GLUT4-mOrange. FSE stimulated glucose uptake; GLUT4 expression and translocation; PM fusion; intracellular Ca2+ elevation; and the phosphorylation of AMPK, Akt, and PKC in L6 cells. GLUT4 translocation was weakened by the AMPK inhibitor compound C, PI3K inhibitor Wortmannin, PKC inhibitor Gö6983, G protein inhibitor PTX/Gallein, and PLC inhibitor U73122. Similarly, in addition to PTX/Gallein and U73122, the IP3R inhibitor 2-APB and a 0 mM Ca2+-EGTA solution partially inhibited the elevation of intracellular Ca2+ levels. BAPTA-AM had a significant inhibitory effect on FSE-mediated GLUT4 activities. In summary, FSE regulates GLUT4 expression and translocation by activating the AMPK, PI3K/Akt, and G protein–PLC–PKC pathways. FSE causes increasing Ca2+ concentration to complete the fusion of GLUT4 vesicles with PM, allowing glucose uptake. Therefore, FSE may be a potential drug for improving T2DM.

Highlights

Diabetes mellitus (DM) is a chronic metabolic disorder resulting from insufficient insulin secretion or insulin dysfunction
To understand whether Folium Sennae (FSE) affected the expression of the glucose regulator glucose transporter 4 (GLUT4), the total protein and mRNA
Of GLUT4 and the mRNA of insulin-regulated aminopeptidase (IRAP) in L6 cells were extracted after stimulation with insulin or FSE

Summary

Introduction

Diabetes mellitus (DM) is a chronic metabolic disorder resulting from insufficient insulin secretion or insulin dysfunction. It may lead to a series of complications such as renal failure, cardiovascular disease, blindness, hypertension, non-alcoholic fatty liver disease (NAFLD), and obesity [1,2]. The global prevalence of DM is on the rise, especially in developing countries [3]. T2DM is the most prevalent form of DM and accounts for more than 90% of the cases of DM [4]. Insulin resistance is the typical feature of T2DM, which causes cells to stop responding adequately to the standard role. While the body continues to produce insulin, the cells in the body become resistant to its effects. Cells cannot effectively process insulin, resulting in hyperglycemia [5,6,7]

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