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High Insulin Levels in KK-Ay Diabetic Mice Cause Increased Cortical Bone Mass and Impaired Trabecular Micro-Structure

College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China
Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of MateriaMedica, Chinese Academy of Medical Sciences, Beijing 100050, China
Authors to whom correspondence should be addressed.
Academic Editor: Charles J. Malemud
Int. J. Mol. Sci. 2015, 16(4), 8213-8226;
Received: 17 March 2015 / Revised: 3 April 2015 / Accepted: 8 April 2015 / Published: 13 April 2015
(This article belongs to the Section Biochemistry)
PDF [1339 KB, uploaded 13 April 2015]


Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia, hyperinsulinemia and complications, including obesity and osteoporosis. Rodents have been widely used to model human T2DM and investigate its effect on the skeleton. We aimed to investigate skeletal alterations in Yellow Kuo Kondo (KK-Ay) diabetic mice displaying high insulin and glucose levels. Bone mineral density (BMD), micro-architecture and bone metabolism-related genes were analyzed. The total femoral areal BMD (aBMD), cortical volumetric BMD (vBMD) and thickness were significantly increased in KK-Ay mice, while the trabecular vBMD and mineralized bone volume/tissue volume (BV/TV), trabecular thickness and number were decreased compared to C57BL mice. The expression of both osteoblast-related genes, such as osteocalcin (OC), bone sialoprotein, Type I Collagen, osteonectin, RUNX2 and OSX, and osteoclast-related genes, such as TRAP and TCIRG, were up-regulated in KK-Ay mice. Correlation analyses showed that serum insulin levels were positively associated with aBMD, cortical vBMD and thickness and negatively associated with trabecular vBMD and micro-architecture. In addition, serum insulin levels were positively related to osteoblast-related and osteoclast-related gene expression. Our data suggest that high insulin levels in KK-Ay diabetic mice may increase cortical bone mass and impair trabecular micro-structure by up-regulating osteoblast-and osteoclast-related gene expression. View Full-Text
Keywords: T2DM; KK-Ay mice; insulin; BMD; bone structure; osteoblast; osteoclast T2DM; KK-Ay mice; insulin; BMD; bone structure; osteoblast; osteoclast

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Fu, C.; Zhang, X.; Ye, F.; Yang, J. High Insulin Levels in KK-Ay Diabetic Mice Cause Increased Cortical Bone Mass and Impaired Trabecular Micro-Structure. Int. J. Mol. Sci. 2015, 16, 8213-8226.

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