Chromium enhances insulin responsiveness via AMPK

Journal article


Hoffman, Nolan John, Penque, Brent A., Habegger, Kirk M., Sealls, Whitney, Tackett, Lixuan and Elmendorf, Jeffrey S.. (2014) Chromium enhances insulin responsiveness via AMPK. Journal of Nutritional Biochemistry. 25(5), pp. 565 - 572. https://doi.org/10.1016/j.jnutbio.2014.01.007
AuthorsHoffman, Nolan John, Penque, Brent A., Habegger, Kirk M., Sealls, Whitney, Tackett, Lixuan and Elmendorf, Jeffrey S.
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.

KeywordsAMP-activated protein kinase; cholesterol; chromium; GLUT4; insulin
Year2014
JournalJournal of Nutritional Biochemistry
Journal citation25 (5), pp. 565 - 572
PublisherElsevier Inc.
ISSN0955-2863
Digital Object Identifier (DOI)https://doi.org/10.1016/j.jnutbio.2014.01.007
Scopus EID2-s2.0-84897940484
Page range565 - 572
Research GroupMary MacKillop Institute for Health Research
Place of publicationUnited States of America
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