GLUT4 Translocation In Cells Research Articles

Blood glucose‐lowering effect of water and ethanolic extracts of Gynura procumbens (Lour.) Merr

ABSTRACTAimGynura procumbens (Lour.) Merr. (GP) has drawn attention as an alternative drug for the treatment of diabetes mellitus. However, while most previous studies were done in diabetic mice to investigate the antidiabetic effect, this study investigated the blood glucose‐lowering action of GP in diet‐induced obese mice and clarified the possible mechanism of the glucose‐lowering action of GP in muscle and adipose cells.MethodsThe mice were divided into four groups (n = 6 in each group) depending on the diet that they received (i.e., the normal diet (ND), normal diet + 1% GP powder (ND + GP), high‐fat diet (HFD), high‐fat diet + 1% GP powder (HFD + GP) groups), and the oral glucose tolerance test (OGTT) was performed after one, three and five months. Immunocytochemistry revealed GLUT4 translocation in cells stably expressing myc‐GLUT4‐ECFP. The effect of GP extracts on the expression of GLUT4 and phosphorylation of 5'‐adenosine monophosphate‐activated protein kinase (AMPK) and Akt/protein kinase B (PKB) in C2C12 (muscle cell) and 3T3‐L1 (adipocyte) cells, was determined by western blot analysis.ResultsThe results showed that the significantly raised serum glucose levels in the HFD group were reduced following treatment with GP powder. Moreover, treatment with the GP extracts promoted GLUT4 membrane translocation more prominently in the C2C12 cells as compared to the 3T3‐L1 cells, whereas GLUT4 expression was significantly increased only in the 3T3‐L1 cells. AMPK phosphorylation was significantly increased by both extracts in both C2C12 cells and 3T3‐L1 cells.ConclusionThe findings of the present study reveal that GP may correct glucose intolerance and both the ethanolic and water extracts of GP have a blood glucose‐lowering effect, possibly via AMPK‐mediated signaling pathways in the muscle and adipose tissues.

Efektivitas Ekstrak Etanol Biji Pinang Terhadap Densitas GLUT4 pada Sel-Sel Otot Rangka Mencit yang Terinduksi Hiperglikemia

Betel nut (Areca catechu) was proven to have antihyperglycemic activity through increased PI3K pathway in the GLUT4 translocation in cells. However, research on the ethanol extract of betel nut in Indonesia is still limited. The main problem in this study was whether the ethanol extract of betel nut could improve glucose tolerance in a two-hour postprandial period and whether the ethanol extract of betel nut could induce GLUT4 translocation in skeletal muscle cells of mice induced hyperglycemia. Glucose tolerance test results showed that treatment of the ethanol extract of betel nut for 24 days with all doses tested: P50,100,150,200 and 250 mg/kg body weight could improve glucose tolerance in a two-hour postprandial period. The protein electrophoresis of that fasting and one hour postprandial state treatments resulted an increase in GLUT4/βActin density ratio of P250 group compared to negative and positive controls. In this case, GLUT4/βActin density ratio of P100,P200 and P250 were higher than that GLUT4/βActin density ratio of P50 and P150. Increased in GLUT4/βActin density ratio showed enhancement of the GLUT4 in skeletal muscle cells in fasting and one hour postprandial state after treated with ethanol extract of betel nut.

PTEN Does Not Modulate GLUT4 Translocation in Rat Adipose Cells under Physiological Conditions

PTEN is a 3′-inositol lipid phosphatase that dephosphorylates products of PI 3-kinase. Since PI 3-kinase is required for many metabolic actions of insulin, we investigated the role of PTEN in insulin-stimulated translocation of GLUT4. In control rat adipose cells, we observed a ∼2-fold increase in cell surface GLUT4 upon maximal insulin stimulation. Overexpression of wild-type PTEN abolished this response to insulin. Translocation of GLUT4 in cells overexpressing PTEN mutants without lipid phosphatase activity was similar to that observed in control cells. Overexpression of PTEN-CBR3 (mutant with disrupted membrane association domain) partially impaired translocation of GLUT4. In Cos-7 cells, overexpression of wild-type PTEN had no effect on ERK2 phosphorylation in response to acute insulin stimulation. However, Elk-1 phosphorylation in response to chronic insulin treatment was significantly decreased. Thus, when PTEN is overexpressed, both its lipid phosphatase activity and subcellular localization play a role in antagonizing metabolic actions of insulin that are dependent on PI 3-kinase but independent of MAP kinase. However, because translocation of GLUT4 in cells overexpressing a dominant inhibitory PTEN mutant (C124S) was similar to that of control cells, we conclude that endogenous PTEN may not modulate metabolic functions of insulin under normal physiological conditions.

Closing in on the cause of insulin resistance and type 2 diabetes.

Closing in on the cause of insulin resistance and type 2 diabetes.