Uchiyama Satoshi, Yamaguchi Masayoshi
Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
Int J Mol Med. 2003 Dec;12(6):949-54.
The effect of zinc acexamate in streptozotocin (STZ)-induced diabetic rats was investigated. Rats received a single subcutaneous administration of STZ (6.0 mg/100 g body weight), and the animals were orally administered once daily for 14 days with zinc acexamate (2.5, 5 or 10 mg/100 g body weight). The administration of STZ caused a significant increase in serum glucose, triglyceride and calcium levels and a significant decrease in body weight, serum zinc and inorganic phosphorus levels, indicating diabetic condition. Moreover, calcium content, alkaline phosphatase activity and deoxyribonucleic acid (DNA) content in the femoral-diaphyseal and -metaphyseal tissues were significantly reduced in STZ-diabetic rats. The change in these serum and bone components of STZ-diabetic rats was significantly restored by the oral administration of zinc acexamate (2.5, 5 or 10 mg Zn/100 g body weight). The restoration of bone components was not seen by the oral administration of zinc sulfate (2.5 mg Zn/100 g) for 14 days. Moreover, when the femoral-diaphyseal and -metaphyseal tissues obtained at 14 days after STZ administration were cultured for 48 h in a medium containing either vehicle or zinc acexamate (10(-5) M), the femoral calcium content and alkaline phosphatase activity were significantly increased in vitro. The effect of zinc acexamate was completely abolished in the presence of cycloheximide (10(-6) M), an inhibitor of protein synthesis. The present study demonstrates that the oral administration of zinc acexamate has a preventive effect on STZ-induced diabetic condition in rats, and that it can restorate bone loss of STZ-induced diabetes in vivo.
研究了醋氨己酸锌对链脲佐菌素(STZ)诱导的糖尿病大鼠的作用。大鼠接受单次皮下注射STZ(6.0mg/100g体重),然后每天口服醋氨己酸锌(2.5、5或10mg/100g体重),持续14天。注射STZ导致血清葡萄糖、甘油三酯和钙水平显著升高,体重、血清锌和无机磷水平显著降低,表明出现糖尿病状态。此外,STZ诱导的糖尿病大鼠股骨骨干和干骺端组织中的钙含量、碱性磷酸酶活性和脱氧核糖核酸(DNA)含量显著降低。口服醋氨己酸锌(2.5、5或10mg锌/100g体重)可显著恢复STZ诱导的糖尿病大鼠这些血清和骨骼成分的变化。口服硫酸锌(2.5mg锌/100g)14天未观察到骨骼成分的恢复。此外,将STZ注射后14天获得的股骨骨干和干骺端组织在含有赋形剂或醋氨己酸锌(10⁻⁵M)的培养基中培养48小时,体外股骨钙含量和碱性磷酸酶活性显著增加。在蛋白质合成抑制剂环己酰亚胺(10⁻⁶M)存在的情况下,醋氨己酸锌的作用完全消失。本研究表明,口服醋氨己酸锌对大鼠STZ诱导的糖尿病状态有预防作用,并且可以在体内恢复STZ诱导的糖尿病导致的骨质流失。