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

Author(s): S. Cheng, W. Y. So, D. Zhang, Q. Cheng, B. J. Boucher, P. S. Leung.

Journal Name: Current Molecular Medicine

Volume 16 , Issue 8 , 2016

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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.

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Article Details

VOLUME: 16
ISSUE: 8
Year: 2016
Page: [747 - 758]
Pages: 12
DOI: 10.2174/1566524016666160920111407
Price: $58

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