Chromium enhances insulin responsiveness via AMPK

Academic Article

Abstract

  • Trivalent chromium (Cr ) is known to improve glucose homeostasis. Cr has been shown to improve plasma membrane-based aspects of glucose transporter GLUT4 regulation and increase activity of the cellular energy sensor 5' AMP-activated protein kinase (AMPK). However, the mechanism(s) by which Cr improves insulin responsiveness and whether AMPK mediates this action is not known. In this study we tested if Cr protected against physiological hyperinsulinemia-induced plasma membrane cholesterol accumulation, cortical filamentous actin (F-actin) loss and insulin resistance in L6 skeletal muscle myotubes. In addition, we performed mechanistic studies to test our hypothesis that AMPK mediates the effects of Cr on GLUT4 and glucose transport regulation. Hyperinsulinemia-induced insulin-resistant L6 myotubes displayed excess membrane cholesterol and diminished cortical F-actin essential for effective glucose transport regulation. These membrane and cytoskeletal abnormalities were associated with defects in insulin-stimulated GLUT4 translocation and glucose transport. Supplementing the culture medium with pharmacologically relevant doses of Cr in the picolinate form (CrPic) protected against membrane cholesterol accumulation, F-actin loss, GLUT4 dysregulation and glucose transport dysfunction. Insulin signaling was neither impaired by hyperinsulinemic conditions nor enhanced by CrPic, whereas CrPic increased AMPK signaling. Mechanistically, siRNA-mediated depletion of AMPK abolished the protective effects of CrPic against GLUT4 and glucose transport dysregulation. Together these findings suggest that the micronutrient Cr , via increasing AMPK activity, positively impacts skeletal muscle cell insulin sensitivity and glucose transport regulation. © 2014 Elsevier Inc. 3+ 3+ 3+ 3+ 3+ 3+ 3+
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Hoffman NJ; Penque BA; Habegger KM; Sealls W; Tackett L; Elmendorf JS
  • Start Page

  • 565
  • End Page

  • 572
  • Volume

  • 25
  • Issue

  • 5