II型糖尿病胰岛素抵抗条件下骨化三醇通过钙离子/CaMKKβ/AMPK诱导肝脏甘油三酯的积累和葡萄糖输出

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

Volume: 16 Issue: 8

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

Affiliation:

关键词: 钙；人肝癌细胞；脂肪生成；糖质新生；非酒精性脂肪性肝病；维生素D

摘要: 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.

Cite this article as:

S. Cheng, W. Y. So, D. Zhang, Q. Cheng, B. J. Boucher, P. S. Leung , Calcitriol Reduces Hepatic Triglyceride Accumulation and Glucose Output Through Ca2+/CaMKKβ/AMPK Activation Under Insulin-Resistant Conditions in Type 2 Diabetes Mellitus, Current Molecular Medicine 2016; 16 (8) . https://dx.doi.org/10.2174/1566524016666160920111407