1,25-Dihydroxy vitamin D3 treatment attenuates osteopenia, and improves bone muscle quality in Goto-Kakizaki type 2 diab
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ORIGINAL ARTICLE
1,25-Dihydroxy vitamin D3 treatment attenuates osteopenia, and improves bone muscle quality in Goto-Kakizaki type 2 diabetes model rats Yanlong Liang1 Yanzhi Liu1,2 Wenxiu Lai1 Minqun Du1 Shuhui Li1 Limin Zhou1 Yulin Mo1 Pan Wang1 Yalin Min1 Liao Cui1 ●
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Received: 26 November 2018 / Accepted: 28 January 2019 © The Author(s) 2019
Abstract Purpose: Osteopenia and skeletal fragility are considered to be the complications associated with type 2 diabetes mellitus (T2DM). The relationship between glucose metabolism, skeletal quality, and vitamin D have not been completely understood. We aimed to demonstrate a comprehensive bone quality profile in a T2DM model subject and to investigate whether 1, 25-dihydroxy vitamin D3 could prevent osteopenia and skeletal fragility in the diabetes model rats. Methods: Daily calcitriol (a 1, 25-dihydroxy vitamin D3 formulation, 0.045 μg/kg/day) treatment was administered to 21week-old male Goto-Kakizaki (GK) rats (a genetic non-obese and non-insulin-dependent spontaneous diabetes rat model) for 20 weeks and the results were compared with those in untreated GK rats, and wild-type animals. Results: Micro-computed tomography, histomorphometry, and bone mineral density analysis demonstrated that T2DM induced significant osteopenia, and impairment of bone microarchitecture and biomechanical properties in GK rats. T2DM also significantly decreased bone formation and increased bone resorption parameters in three regions of the skeleton (proximal tibia, mid-shaft of the tibia, and lumbar vertebrae), and increased carboxy-terminal type I collagen crosslinks, tartrate-resistant acid phosphatase, muscle ubiquitin C, and bone thioredoxin interacting protein (TXNIP) expression. Calcitriol treatment significantly alleviated bone loss, and improved bone microarchitecture and biomechanical properties and also decreased serum glucose and glycated serum protein levels. Biomarkers of bone formation were significantly increased, while muscle ubiquitin C and bone TXNIP expression were significantly decreased following calcitriol treatment. Conclusions: These results suggest that 1,25-dihydroxy vitamin D3 treatment effectively attenuates osteopenia, and improves bone and muscle quality in GK type 2 diabetes model rats. Keywords Type 2 diabetes Vitamin D3 Bone Osteopenia Calcitriol GK rat ●
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Introduction
These authors contributed equally: Yanlong Liang, Yanzhi Liu * Liao Cui [email protected] 1
Guangdong Key laboratory for Research and Development of Natural Drugs, Department of Pharmacology, Guangdong Medical University, 524023 Zhanjiang, China
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Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 518055 Shenzhen, China
Type 2 diabetes mellitus (T2DM) is becoming an increasingly prevalent disease worldwide, according to the 2016 report of the World Health Organization [1], 422 million people worldwide have diabetes, and T
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