S Cheng, W Y So, D Zhang, Q Cheng, B J Boucher, P S Leung1. 1. 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.
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.
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.
Authors: Wafaa M Abdel-Rehim; Rasha A El-Tahan; Mennatullah A El-Tarawy; Rowaida R Shehata; Maher A Kamel Journal: Mol Cell Biochem Date: 2018-06-16 Impact factor: 3.396
Authors: William B Grant; Fatme Al Anouti; Barbara J Boucher; Erdinç Dursun; Duygu Gezen-Ak; Edward B Jude; Tatiana Karonova; Pawel Pludowski Journal: Nutrients Date: 2022-02-02 Impact factor: 5.717