Abstract
Induction of GLUT4 translocation in the absence of insulin is considered a key concept to decrease elevated blood glucose levels in diabetics. Due to the lack of pharmaceuticals that specifically increase the uptake of glucose from the blood circuit, application of natural compounds might be an alternative strategy. However, the effects and mechanisms of action remain unknown for many of those substances. For this study we investigated extracts prepared from seven different plants, which have been reported to exhibit anti-diabetic effects, for their GLUT4 translocation inducing properties. Quantitation of GLUT4 translocation was determined by total internal reflection fluorescence (TIRF) microscopy in insulin sensitive CHO-K1 cells and adipocytes. Two extracts prepared from purslane (Portulaca oleracea) and tindora (Coccinia grandis) were found to induce GLUT4 translocation, accompanied by an increase of intracellular glucose concentrations. Our results indicate that the PI3K pathway is mainly responsible for the respective translocation process. Atomic force microscopy was used to prove complete plasma membrane insertion. Furthermore, this approach suggested a compound mediated distribution of GLUT4 molecules in the plasma membrane similar to insulin stimulated conditions. Utilizing a fluorescent actin marker, TIRF measurements indicated an impact of purslane and tindora on actin remodeling as observed in insulin treated cells. Finally, in-ovo experiments suggested a significant reduction of blood glucose levels under tindora and purslane treated conditions in a living organism. In conclusion, this study confirms the anti-diabetic properties of tindora and purslane, which stimulate GLUT4 translocation in an insulin-like manner.
Highlights
As of 2013, an estimated 381 million people had diabetes mellitus
We have recently shown that total internal reflection fluorescence (TIRF) microscopy is a superior tool for the quantitation of glucose transporter 4 (GLUT4) translocation in living cells [29]
In comparison to the treatment with 100 nM insulin, which led to an increase of the GFP-signal of ~36% within 10 minutes, incubation with 50 mg/l purslane extract or the polyphenol mixture (PP60) for the same time period resulted in a major increase (~53% and ~137%, respectively; Fig 1C)
Summary
As of 2013, an estimated 381 million people had diabetes mellitus. Its prevalence has dramatically increased and results in a considerably higher rate of mortality worldwide [1]. Type 2 diabetes mellitus (T2DM) makes up about 90% of all cases and is caused by a combination of inadequate compensatory insulin secretion and a lack of functional insulin receptors, PLOS ONE | DOI:10.1371/journal.pone.0148109 January 28, 2016
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