Objectives: 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
Methods: 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.
Results: 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 β (CaMKKβ) pathway, contributing to the reductions in hepatic triglyceride
accumulation and glucose output. Calcitriol also induced AMPK/ACC phosphorylation in liver
of db/db mice.
Conclusion: 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.