TY - JOUR
T1 - Biomolecular Characterization of Putative Antidiabetic Herbal Extracts
AU - Stadlbauer, Verena
AU - Haselgrübler, Renate
AU - Lanzerstorfer, Peter
AU - Plochberger, Birgit
AU - Borgmann, Daniela Martina
AU - Jacak, Jaroslaw
AU - Winkler, Stephan
AU - Schröder, Klaus
AU - Höglinger, Otmar
AU - Weghuber, Julian
N1 - Funding Information:
This work was funded by the Austrian Research Promotion Agency (FFG; project number 850681) and University of Applied Sciences Upper Austria Basic Funding initiative (project GlucoSTAR). BioMed zet Life Science GmbH is funded by the federal state auf Upper Austria. BioMed zet Life Science GmbH provided support in the form of salaries for author KS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the author contributions section. We thank Manoj Kumar Bhat (National Centre for Cell Science, NCCS Complex, Pune University, India) for providing CHO-K1 hIR/GLUT4-myc-GFP cell line, Alan Saltiel (University of Michigan, USA) for providing 3T3-L1 GLUT4-GFP cells, and Torsten Grothe (Frutarom Industries Ltd.) for providing the purslane extract. The Lifeact-tdTomato was a kind gift from Weiping Han (Singapore Bioimaging Consortium).
Publisher Copyright:
© 2016 Stadlbauer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
KW - Adipocytes/drug effects
KW - Animals
KW - CHO Cells
KW - Chick Embryo
KW - Cricetulus
KW - Cucurbitaceae/chemistry
KW - Glucose Transporter Type 4/metabolism
KW - Glucose/metabolism
KW - Hypoglycemic Agents/chemistry
KW - Phosphatidylinositol 3-Kinases/metabolism
KW - Plant Extracts/chemistry
KW - Portulaca/chemistry
KW - Protein Transport/drug effects
UR - http://www.scopus.com/inward/record.url?scp=84958225521&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0148109
DO - 10.1371/journal.pone.0148109
M3 - Article
C2 - 26820984
SN - 1932-6203
VL - 11
SP - e0148109
JO - PLoS ONE
JF - PLoS ONE
IS - 1
M1 - e0148109
ER -