Chromium Enhances Insulin Responsiveness via AMPK
dc.contributor.author | Hoffman, Nolan J. | |
dc.contributor.author | Penque, Brent A. | |
dc.contributor.author | Habegger, Kirk M. | |
dc.contributor.author | Sealls, Whitney | |
dc.contributor.author | Tackett, Lixuan | |
dc.contributor.author | Elmendorf, Jeffrey S. | |
dc.contributor.department | Department of Cellular & Integrative Physiology, IU School of Medicine | en_US |
dc.date.accessioned | 2016-02-03T17:46:23Z | |
dc.date.available | 2016-02-03T17:46:23Z | |
dc.date.issued | 2014-05 | |
dc.description.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. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Hoffman, N. J., Penque, B. A., Habegger, K. M., Sealls, W., Tackett, L., & Elmendorf, J. S. (2014). Chromium Enhances Insulin Responsiveness via AMPK. The Journal of Nutritional Biochemistry, 25(5), 565–572. http://doi.org/10.1016/j.jnutbio.2014.01.007 | en_US |
dc.identifier.issn | 0955-2863 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/8238 | |
dc.language.iso | en_US | en_US |
dc.publisher | Elsevier | en_US |
dc.relation.isversionof | 10.1016/j.jnutbio.2014.01.007 | en_US |
dc.relation.journal | The Journal of nutritional biochemistry | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | AMP-Activated Protein Kinases | en_US |
dc.subject | metabolism | en_US |
dc.subject | Chromium | en_US |
dc.subject | pharmacology | en_US |
dc.subject | Muscle Fibers, Skeletal | en_US |
dc.subject | drug effects | en_US |
dc.subject | Cholesterol | en_US |
dc.subject | GLUT4 | en_US |
dc.subject | Insulin | en_US |
dc.title | Chromium Enhances Insulin Responsiveness via AMPK | en_US |
dc.type | Article | en_US |