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J Nutr Biochem. 2014 May;25(5):565-72. doi: 10.1016/j.jnutbio.2014.01.007. Epub 2014 Feb 20.

Chromium enhances insulin responsiveness via AMPK.

Author information

1
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
2
Department of Biochemistry and Molecular Biology, Center for Diabetes Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Medicine - Endocrinology, Diabetes & Metabolism University of Alabama at Birmingham, Birmingham, AL 35294, USA.
3
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Biochemistry and Molecular Biology, Center for Diabetes Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: jelmendo@iupui.edu.

Abstract

Trivalent chromium (Cr(3+)) is known to improve glucose homeostasis. Cr(3+) 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(3+) improves insulin responsiveness and whether AMPK mediates this action is not known. In this study we tested if Cr(3+) 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(3+) 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(3+) 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(3+), via increasing AMPK activity, positively impacts skeletal muscle cell insulin sensitivity and glucose transport regulation.

KEYWORDS:

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

PMID:
24725432
PMCID:
PMC4030743
DOI:
10.1016/j.jnutbio.2014.01.007
[Indexed for MEDLINE]
Free PMC Article

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