Chromium enhances insulin responsiveness via AMPK

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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

Fingerprint

AMP-Activated Protein Kinases
Chromium
Insulin
Glucose
Actins
Cholesterol
Skeletal Muscle Fibers
Hyperinsulinism
Cell membranes
Membranes
Muscle
Insulin Resistance
Skeletal Muscle
Cell Membrane
Facilitative Glucose Transport Proteins
Micronutrients
Muscle Cells
Small Interfering RNA
Culture Media
Homeostasis

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. (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

Chromium enhances insulin responsiveness via AMPK. / Hoffman, Nolan J.; Penque, Brent A.; Habegger, Kirk M.; Sealls, Whitney; Tackett, Lixuan; Elmendorf, Jeffrey.

In: Journal of Nutritional Biochemistry, Vol. 25, No. 5, 2014, p. 565-572.

Research output: Contribution to journalArticle

Hoffman, NJ, Penque, BA, Habegger, KM, Sealls, W, Tackett, L & Elmendorf, J 2014, 'Chromium enhances insulin responsiveness via AMPK', Journal of Nutritional Biochemistry, vol. 25, no. 5, pp. 565-572. https://doi.org/10.1016/j.jnutbio.2014.01.007
Hoffman, Nolan J. ; Penque, Brent A. ; Habegger, Kirk M. ; Sealls, Whitney ; Tackett, Lixuan ; Elmendorf, Jeffrey. / Chromium enhances insulin responsiveness via AMPK. In: Journal of Nutritional Biochemistry. 2014 ; Vol. 25, No. 5. pp. 565-572.
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