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Calcitriol Reduces Hepatic Triglyceride Accumulation and Glucose Output Through Ca2+/CaMKKβ/AMPK Activation Under Insulin-Resistant Conditions in Type 2 Diabetes Mellitus

[ Vol. 16 , Issue. 8 ]

Author(s):

S. Cheng, W. Y. So, D. Zhang, Q. Cheng, B. J. Boucher and P. S. Leung   Pages 747 - 758 ( 12 )

Abstract:


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 diabetes.

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.

Keywords:

Calcium, HepG2 cells, lipogenesis, gluconeogenesis, non-alcoholic fatty liver disease, vitamin D.

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.



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