title: Calcitriol Reduces Hepatic Triglyceride Accumulation and Glucose Output Through Ca2+/CaMKK&#946;/AMPK Activation Under Insulin-Resistant Conditions in Type 2 Diabetes Mellitus.
abstract: The present study was designed to investigate the effects of calcitriol (the active hormonal metabolite of vitamin D) on hepatic metabolic abnormalities in type 2 diabetes.
  
  
  
  Type 2 diabetic db/db mice were used to investigate the effects of calcitriol on hepatic and systemic metabolic disorders. HepG2 cells cultured in insulin-resistant conditions were used to examine the potential mechanisms for calcitriol-induced changes in hepatic lipid and glucose metabolism.
  
  
  
  8-week calcitriol treatment ameliorated abnormal hepatic lipid and glucose production in db/db mice. In HepG2 cells under insulin-resistant condition, calcitriol increased cytosolic calcium concentration and induced 5'-AMP-activated protein kinase/acetyl-CoAcarboxylase (AMPK/ACC) phosphorylation via the Ca2+/calmodulin-dependent protein kinase kinase &#946; (CaMKK&#946;) pathway, contributing to the reductions in hepatic triglyceride accumulation and glucose output. Calcitriol also induced AMPK/ACC phosphorylation in liver of db/db mice.
  
  
  
  Our data indicate that calcitriol, at above-physiological serum concentrations, reduces hepatic triglyceride accumulation and glucose output, at least in part through activation of Ca2+/CaMKKβ/AMPK under insulin-resistant condition.
authors.forename: S
authors.initials: S
authors.lastname: Cheng
authors.forename: W Y
authors.initials: WY
authors.lastname: So
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Cheng
authors.forename: B J
authors.initials: BJ
authors.lastname: Boucher
authors.affiliation: Room 609A, Lo Kwee- Seong Integrated Biomedical Sciences Building, School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. psleung@cuhk.edu.hk.
authors.forename: P S
authors.initials: PS
authors.lastname: Leung
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D010766:Phosphorylation; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D007328:Insulin; D014280:Triglycerides; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D055372:AMP-Activated Protein Kinases; D002117:Calcitriol; D005947:Glucose; D002118:Calcium