Molecular process of glucose uptake and glycogen storage due to hamamelitannin via insulin signalling cascade in glucose
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ORIGINAL ARTICLE
Molecular process of glucose uptake and glycogen storage due to hamamelitannin via insulin signalling cascade in glucose metabolism Praveen Kumar Issac1 · Ajay Guru1 · Sri Snehaa Chandrakumar2 · Christy Lite3 · N. T. Saraswathi4 · Mariadhas Valan Arasu5 · Naif Abdullah Al‑Dhabi5 · Aziz Arshad6,7 · Jesu Arockiaraj1 Received: 3 June 2020 / Accepted: 10 August 2020 © Springer Nature B.V. 2020
Abstract Understanding the mechanism by which the exogenous biomolecule modulates the GLUT-4 signalling cascade along with the information on glucose metabolism is essential for finding solutions to increasing cases of diabetes and metabolic disease. This study aimed at investigating the effect of hamamelitannin on glycogen synthesis in an insulin resistance model using L6 myotubes. Glucose uptake was determined using 2-deoxy-d-[1-3H] glucose and glycogen synthesis were also estimated in L6 myotubes. The expression levels of key genes and proteins involved in the insulin-signaling pathway were determined using real-time PCR and western blot techniques. The cells treated with various concentrations of hamamelitannin (20 µM to 100 µM) for 24 h showed that, the exposure of hamamelitannin was not cytotoxic to L6 myotubes. Further the 2-deoxy-d[1-3H] glucose uptake assay was carried out in the presence of wortmannin and Genistein inhibitor for studying the GLUT-4 dependent cell surface recruitment. Hamamelitannin exhibited anti-diabetic activity by displaying a significant increase in glucose uptake (125.1%) and glycogen storage (8.7 mM) in a dose-dependent manner. The optimum concentration evincing maximum activity was found to be 100 µm. In addition, the expression of key genes and proteins involved in the insulin signaling pathway was studied to be upregulated by hamamelitannin treatment. Western blot analysis confirmed the translocation of GLUT-4 protein from an intracellular pool to the plasma membrane. Therefore, it can be conceived that hamamelitannin exhibited an insulinomimetic effect by enhancing the glucose uptake and its further conversion into glycogen by regulating glucose metabolism. Keywords Hamamelitannin · Insulin signalling · Molecular process · Glycogen synthesis · Type II diabetes mellitus Abbreviations DM Diabetes mellitus T2DM Type 2 diabetic mellitus IRS insulin receptor substrate PI3Ks phosphoinositide 3-kinases GLUT-4 glucose transporter type 4 GS Glycogen synthase ROS Reactive oxygen species DMEM Dulbecco’s modified eagle’s medium NCCS National Center for Cell Science Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05728-5) contains supplementary material, which is available to authorized users. * Jesu Arockiaraj [email protected] Extended author information available on the last page of the article
PBS Phosphate buffer saline DMSO dimethylsulfoxide KRPH Krebs–Ringer phosphate buffer solution IRTK Insulin receptor tyrosine kinase DEPC Diethyl pyrocarbonate IRβ Insulin receptor β GSK-3β Glycog
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