title: Influence of vitamin D treatment on transcriptional regulation of insulin-sensitive genes.
abstract: BACKGROUND
  Obesity is a risk factor for diabetes and metabolic syndrome, which are characterized by insulin resistance. Inflammation is a co-morbid condition associated with obesity. Vitamin D, besides being a transcriptional regulator, is an inflammation suppressor. However, the role of vitamin D in alleviating obesity-induced insulin resistance is still not well understood.
  
  
  METHODS
  The influence of vitamin D treatment on the transcriptional level of insulin receptor (IR), insulin receptor substrate (IRS-1), glucose transporter type 4 (GLUT-4), and vitamin D receptor (VDR) in insulin target tissues of liver, adipose, and muscle of mice fed on a high-fat diet (HFD) or low-fat diet (LFD) was studied by quantitative RT-PCR.
  
  
  RESULTS
  A gradual weight reduction was observed in HFD-fed mice treated with vitamin D compared to a steady weight increase in control animals (P<0.01). In HFD mice, vitamin D decreased VDR expression to 0.5-fold in muscle (P=0.002), and increased it to 3.6-fold in the liver (P<0.001); however, VDR transcription was unaltered in adipose tissue. Similarly, vitamin D did not influence tissue expression of IR in either LFD- or HFD-fed mice. Muscle IRS-1 transcription level was upregulated to 2.4-fold (P=0.005) in HFD mice, whereas it was reduced to 0.15-fold in liver tissue (P<0.001). Vitamin D treatment had no effect on GLUT-4 transcript levels in any of the tissues under HFD conditions.
  
  
  CONCLUSIONS
  Vitamin D treatment influenced the expression of insulin-sensitive genes in a tissue-specific fashion. On the basis of the present findings, vitamin D does not aid glucose transport across cells of liver and adipose tissues, the major insulin-sensitive tissues, in HFD-fed mice; however, it appears to enhance the intracellular mechanisms of insulin action mediated by IRS-1 and VDR in muscle tissue.
authors.affiliation: Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. alkharfy@ksu.edu.sa
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Alkharfy
authors.forename: Nasser M
authors.initials: NM
authors.lastname: Al-Daghri
authors.forename: Sobhy M
authors.initials: SM
authors.lastname: Yakout
authors.forename: Tajamul
authors.initials: T
authors.lastname: Hussain
authors.forename: Abdul Khader
authors.initials: AK
authors.lastname: Mohammed
authors.forename: Soundararajan
authors.initials: S
authors.lastname: Krishnaswamy
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology*; D059305:Diet, High-Fat / Q000009:adverse effects; D051275:Glucose Transporter Type 4 / Q000235:genetics; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D011972:Receptor, Insulin / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics; D014018:Tissue Distribution; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D018167:Receptors, Calcitriol; C495693:Slc2a4 protein, mouse; D011972:Receptor, Insulin; D002117:Calcitriol