Chromium picolinate positively influences the glucose transporter system via affecting cholesterol homeostasis in adipocytes cultured under hyperglycemic diabetic conditions.
Since trivalent chromium (Cr(3+)) enhances glucose metabolism, interest in the use of Cr(3+)as a therapy for type 2 diabetes has grown in the mainstream medical community. Moreover, accumulating evidence suggests that Cr(3+) 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 Cr(3+)-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.
Pattar
Guruprasad R
GR
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Center for Diabetes Research, Indianapolis, IN 46202, United States.
Tackett
Lixuan
L
Liu
Ping
P
Elmendorf
Jeffrey S
JS
D041721:3T3-L1 Cells; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D017608:Chromium Compounds / Q000737:chemistry / Q000494:pharmacology*; D003470:Culture Media / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D004586:Electrophoresis / Q000379:methods; D005947:Glucose / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D015151:Immunoblotting; D051379:Mice; D010848:Picolinic Acids / Q000737:chemistry / Q000494:pharmacology*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D017608:Chromium Compounds; D003470:Culture Media; D051246:Glucose Transport Proteins, Facilitative; D051275:Glucose Transporter Type 4; D010848:Picolinic Acids; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D002784:Cholesterol; D005947:Glucose; C030614:picolinic acid