Acute administration of diosgenin or dioscorea improves hyperglycemia with increases muscular steroidogenesis in STZ-induced type 1 diabetic rats
Acute administration of diosgenin or dioscorea improves hyperglycemia with increases muscular steroidogenesis in STZ-induced type 1 diabetic rats
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DOI：
10.1016/j.jsbmb.2014.02.020
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发表时间：
2014-09
期刊：
影响因子：
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通讯作者：
K. Sato;S. Fujita;M. Iemitsu
中科院分区：
文献类型：
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作者：
K. Sato;S. Fujita;M. Iemitsu
急性脱氢表雄酮（DHEA）给药可改善链脲佐菌素（STZ）诱导的1型糖尿病大鼠的高血糖。薯蓣皂苷元是一种结构上类似于DHEA（脱氢表雄酮）的类固醇，在diabetrea中含量很高;然而，目前尚不清楚这种天然产物是否通过增加肌肉GLUT 4信号传导来改善1型糖尿病模型大鼠的高血糖症。注射STZ 1周后，每隔30 min从尾静脉取血测量空腹血糖水平，共150 min，注射薯蓣皂苷元或双胍（3 mg/kg）后。第二天，在注射薯蓣皂苷元或双胍后150分钟切除肌肉。注射薯蓣皂苷元或双胍后120 min，血清DHEA水平显著升高，同时血糖水平显著降低。此外，GLUT 4易位，以及Akt和PKC β/λ的磷酸化，通过薯蓣皂苷元或双胍施用显著增加。然而，薯蓣皂苷元和双胍的这些作用被5α-还原酶抑制剂阻断，所述5α-还原酶抑制剂抑制睾酮合成脱氢睾酮（DHT）。此外，在给药后150 min观察到血糖水平、GLUT 4易位水平和肌肉性类固醇激素水平之间存在显著相关性。这些结果表明，薯蓣皂苷元诱导的DHEA水平的增加可能有助于通过激活肌肉GLUT 4信号通路在1型糖尿病模型大鼠中改善高血糖。
Acute dehydroepiandrosterone (DHEA) administration improves hyperglycemia in rats with streptozotocin (STZ)-induced type 1 diabetes mellitus. Diosgenin, a steroid structurally similar to DHEA (dehydroepiandrosterone), is contained highly levels in dioscorea; however, it is still unclear whether this natural product improves hyperglycemia in the type 1 diabetes model rats through an increase muscular GLUT4 signaling. After 1 week of STZ injection, fasting glucose level was measured in blood taken from the tail vein every 30 min for 150 min after injection of diosgenin or dioscorea (3 mg/kg). On another day, muscle was resected 150 min after diosgenin or dioscorea injections. Serum DHEA level increased significantly 120 min after diosgenin or dioscorea injections; concomitantly, blood glucose level decreased significantly. Moreover, GLUT4 translocation, as well as phosphorylation of Akt and PKC ζ/λ, increased significantly by diosgenin or dioscorea administration. However, these effects of diosgenin and dioscorea were blocked by a 5α-reductase inhibitor that inhibits synthesizing dehydrotestosterone (DHT) from testosterone. Additionally, significant correlations were observed between blood glucose level, GLUT4 translocation level, and muscular sex steroid hormone level 150 min after the administrations. These results suggest that the diosgenin-induced increase in the DHEA level may contribute to the improvement of hyperglycemia by activating the muscular GLUT4 signaling pathway in type 1 diabetes model rats.