Research Article: Effects of voluntary running exercise on bone histology in type 2 diabetic rats

Date Published: February 15, 2018

Publisher: Public Library of Science

Author(s): Yuri Takamine, Noriko Ichinoseki-Sekine, Takamasa Tsuzuki, Toshinori Yoshihara, Hisashi Naito, Joseph M Wallace.


The incidence of obesity in children and adolescents, which may lead to type 2 diabetes, is increasing. Exercise is recommended to prevent and improve diabetes. However, little is known about the bone marrow environment at the onset of diabetes in the young, and it is unclear whether exercise training is useful for maintaining bone homeostasis, such as mechanical and histological properties. Thus, this study clarified the histological properties of bone and whether exercise contributes to maintaining bone homeostasis at the onset of type 2 diabetes in rats. Four-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF; n = 21) rats as a diabetic model and Long-Evans Tokushima Otsuka (LETO; n = 18) rats as a control were assigned randomly to four groups: the OLETF sedentary group (O-Sed; n = 11), OLETF exercise group (O-Ex; n = 10), LETO sedentary group (L-Sed; n = 9), and LETO exercise group (L-Ex; n = 9). All rats in the exercise group were allowed free access to a steel running wheel for 20 weeks (5–25 weeks of age). In the glucose tolerance test, blood glucose level was higher in the O-Sed group than that in the L-Sed and L-Ex groups, and was markedly suppressed by the voluntary running exercise of O-Ex rats. The energy to fracture and the two-dimensional bone volume at 25 weeks of age did not differ significantly among the groups, though the maximum breaking force and stiffness were lower in OLETF rats. However, bone marrow fat volume was greater in O-Sed than that in L-Sed and L-Ex rats, and was markedly suppressed by wheel running in the O-Ex rats. Our results indicate that exercise has beneficial effects not only for preventing diabetes but also on normal bone remodeling at an early age.

Partial Text

Diabetes mellitus, especially type 2 diabetes, is increasing worldwide [1]. Diabetics are at risk of complications such as diabetic retinopathy, nephropathy, and neuropathy, which may reduce their quality of life. Currently, the incidence of obesity in children and adolescents is increasing, which may lead to type 2 diabetes. Poor fitness habits or excessive food intake during youth may be related to the increasing incidence of diabetes.

Obese and diabetic patients have a high fracture risk [21]. The increased fracture risk in diabetes may be due to increasing bone fragility caused by diabetes or an increased incidence of falling, which is related to diabetic complications [22]. Several studies have suggested that bone fragility in diabetes is caused by adiposity, insulin resistance, fatty acid composition, and hormones [23–24]. Marrow fat may negatively affect bone fragility in diabetes. The accumulation of marrow fat affects the balance of bone turnover, which may lead to a decrease in bone volume or bone quality [25].

In conclusion, our results demonstrate that the onset of type 2 diabetes did not affect bone volume, while marrow fat accumulated. This accumulation of bone marrow fat was inhibited by 20 weeks of voluntary running exercise, which also prevented the onset of diabetes in OLETF rats, suggesting that exercise has beneficial effects not only on the prevention of diabetes but also on normal bone remodeling at an early age.




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