Chromium picolinate positively influences the glucose transporter system via affecting cholesterol homeostasis in adipocytes cultured under hyperglycemic diabetic conditions

Guruprasad R. Pattar, Lixuan Tackett, Ping Liu, Jeffrey S. Elmendorf

Research output: Contribution to journalArticle

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Abstract

Since trivalent chromium (Cr3+) enhances glucose metabolism, interest in the use of Cr3+as a therapy for type 2 diabetes has grown in the mainstream medical community. Moreover, accumulating evidence suggests that Cr3+ may also benefit cardiovascular disease (CVD) and atypical depression. We have found that cholesterol, a lipid implicated in both CVD and neurodegenerative disorders, also influences cellular glucose uptake. A recent study in our laboratory shows that exposure of 3T3-L1 adipocytes to chromium picolinate (CrPic, 10 nM) induces a loss of plasma membrane cholesterol. Concomitantly, accumulation of intracellularly sequestered glucose transporter GLUT4 at the plasma membrane was dependent on the CrPic-induced cholesterol loss. Since CrPic supplementation has the greatest benefit on glucose metabolism in hyperglycemic insulin-resistant individuals, we asked here if the CrPic effect on cells was glucose-dependent. We found that GLUT4 redistribution in cells treated with CrPic occurs only in cells cultured under high glucose (25 mM) conditions that resemble the diabetic-state, and not in cells cultured under non-diabetic (5.5 mM glucose) conditions. Examination of the effect of CrPic on proteins involved in cholesterol homeostasis revealed that the activity of sterol regulatory element-binding protein (SREBP), a membrane-bound transcription factor ultimately responsible for controlling cellular cholesterol balance, was upregulated by CrPic. In addition, ABCA1, a major player in mediating cholesterol efflux was decreased, consistent with SREBP transcriptional repression of the ABCA1 gene. Although the exact mechanism of Cr3+-induced cholesterol loss remains to be determined, these cellular responses highlight a novel and significant effect of chromium on cholesterol homeostasis. Furthermore, these findings provide an important clue to our understanding of how chromium supplementation might benefit hypercholesterolemia-associated disorders.

Original languageEnglish (US)
Pages (from-to)93-100
Number of pages8
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume610
Issue number1-2
DOIs
StatePublished - Nov 7 2006

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Keywords

  • Cholesterol
  • Chromium picolinate
  • GLUT4

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Genetics

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