Redox signal-mediated TRPM2 promotes Ang II-induced adipocyte insulin resistance via Ca2+ -dependent CaMKII/JNK cascade

Metabolism: Clinical and Experimental
Min GaoXiao-Yan Li

Abstract

Redox-sensitive transient receptor potential melastatin 2 (TRPM2) is a Ca2+-permeable, nonselective cation channel which plays a crucial role in various physiological processes. However, little is known whether TRPM2 is involved in adipocyte dysfunction during hypertension. In the present study, we determined the role of TRPM2 in angiotensin II (Ang II)-induced insulin resistance in adipocytes and the underlying mechanisms. Ang II-induced adipocyte insulin resistant model was conducted. Data from Ang II-induced hypertensive mice were used to measure the effects of TRPM2 inhibitor on insulin resistance in vivo. Whole-cell patch clamp technique, intracellular Ca2+ concentration measurement, glucose uptake assay, western blot, cDNA and siRNA transfection were employed to investigate the TRPM2/Ca2+/CaMKII/JNK signaling. Ang II rose a cation current similar to that activated by hydrogen peroxide (H2O2) or ADP-ribose (ADPR), which was blocked by TRPM2 inhibitor or TRPM2 siRNA in adipocytes. Knockdown of TRPM2 significantly improved the lowered insulin sensitivity induced by Ang II, including insulin stimulated glucose uptake, phosphorylation of IRS1 and Akt, interaction between IR and IRS1 and the membrane translocation of GLUT4, whe...Continue Reading

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