"Purpose: OLETF rat is a model of Type II DM. Bone metabolism has influenced with hormones, growth factors, and cytokines that orchestrate the activities of both osteoclast and osteoblast cells. Type II DM influences bone metabolism and Neuropeptides-leptin and NPY2 receptor’s in hypothalamic control bone formation with osteoblast activity. We tried to distinct alteration of bone metabolism in OLETF rat from 8wks to 52wks. Animals and treatment: Serum samples were collected in eleven male OLETF and LETO (control) rats, femoral BMD and percent body fat were measured in 8, 25, 40, 52wks of age. In 25wks of age, all the OLETF rats developed Type II DM. In 52wks of age, rats were sacrificed and brain sections were made for immunohistochemistry. Hormones, growth factors and bone markers were measured by radioimmunoassay. Results: Body weight and percent body fat in OLETF rat were higher than that of LETO rat in whole time (p<0.001); but BMD was lower than control (p<0.05) from 40wks of age. OLETF rat hypothalamic arcuate neuron cell NPY2 receptor were strongly pattern expressed than LETO rat. OLETF rat testosterone was decreased in 25wks and significantly lower in 40 and 52wks (p<0.05); serum leptin and IGF-I levels were higher (p<0.05) in whole time; insulin levels were higher from 8wks to 40wks(p<0.05), but in 52wks lower (p<0.05) than LETO rat; free T4 were higher in 8wks and 25wks (p<0.05), but in 40wks there was no difference, in 52wks lower than LETO rat; corticosterone level was lower in 8wks (p<0.05), but higher in 25wks, 40wks, and 52wk (p<0.05). OLETF rat serum CTx was higher (p<0.05), but OPG was lower (p<0.05) in 40wks and 52wks. Conclusion: OLETF rat had low bone density after 40wks of age and this finding could be correlated with low level of testosterone, high level of corticosterone and leptin in serum, and also NPY2-R over-expression in hypothalamic arcuate nuclei. "
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