Chromium enhances insulin responsiveness via AMPK

Nolan J. Hoffman, Brent A. Penque, Kirk M. Habegger, Whitney Sealls, Lixuan Tackett, Jeffrey S. Elmendorf

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Trivalent chromium (Cr3+) is known to improve glucose homeostasis. Cr3+ 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 Cr3+ improves insulin responsiveness and whether AMPK mediates this action is not known. In this study we tested if Cr3+ 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 Cr3+ 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 Cr3+ 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 Cr3+, via increasing AMPK activity, positively impacts skeletal muscle cell insulin sensitivity and glucose transport regulation.

Original languageEnglish (US)
Pages (from-to)565-572
Number of pages8
JournalJournal of Nutritional Biochemistry
Volume25
Issue number5
DOIs
StatePublished - May 2014

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Keywords

  • AMP-activated protein kinase
  • Cholesterol
  • Chromium
  • GLUT4
  • Insulin

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Hoffman, N. J., Penque, B. A., Habegger, K. M., Sealls, W., Tackett, L., & Elmendorf, J. S. (2014). Chromium enhances insulin responsiveness via AMPK. Journal of Nutritional Biochemistry, 25(5), 565-572. https://doi.org/10.1016/j.jnutbio.2014.01.007