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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Role of insulin on jejunal PepT1 expression and function regulation in diabetic male and female rats.
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Role of insulin on jejunal PepT1 expression and function regulation in diabetic male and female rats.

机译:胰岛素对糖尿病雄性和雌性大鼠空肠PepT1表达和功能调节的作用。

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摘要

The aim of this study was to determine whether the jejunal oligopeptide transporter PepT1 is regulated by insulin and whether this regulation is sex-dependent in type 1 diabetic rats. PepT1 expression, real-time polymerase chain reaction, and Western blots were performed using jejunal segments from 4 groups of male and female rats: normal (nondiabetic), insulin-treated nondiabetic, streptozotocin (STZ)-induced diabetic (type 1 diabetes), and insulin-treated diabetic models. Furthermore, the same segments from all groups underwent perfusion to assess uptake of the dipeptide glycylsarcosine through PepT1. Our results showed that insulin treatment of nondiabetic female rats decreased blood glucose level but did not affect nondiabetic male rats. In both male and female diabetic rats, insulin did not completely decrease blood glucose level. Insulin treatment decreased PepT1 mRNA level in nondiabetic male rats and increased mRNA level in nondiabetic female rats without affecting the PepT1 protein level in either sex. Inducing diabetes with STZ increased PepT1 mRNA and protein levels in female rats; however, in diabetic male rats, the increase in mRNA level was accompanied by a decrease in PepT1 protein level. Treatment of diabetic male rats with insulin partially reversed the effect of diabetes on PepT1 mRNA and protein levels, whereas the same treatment completely restored both PepT1 mRNA and protein to control levels in insulin-treated diabetic female rats. In both nondiabetic male and female rats, insulin treatment had no effect on PepT1 influx rate, and STZ treatment decreased the transporter influx rate. Treatment of diabetic male and female rats with insulin significantly increased PepT1 influx rate; however, complete recovery was found only in diabetic female rats. These results clearly show that insulin and diabetes affected blood glucose level as well as PepT1 activity, expression, and protein levels in a sex-dependent manner. These results suggest that a factor, probably estrogen, could be responsible for the sex-dependent effects of diabetes and insulin in PepT1 level and activity.
机译:这项研究的目的是确定空肠寡肽转运蛋白PepT1是否受胰岛素调节,以及该调节是否在1型糖尿病大鼠中是性别依赖性的。 PepT1表达,实时聚合酶链反应和Western印迹使用4组雄性和雌性大鼠的空肠段进行:正常(非糖尿病),胰岛素治疗的非糖尿病,链脲佐菌素(STZ)诱导的糖尿病(1型糖尿病),和胰岛素治疗的糖尿病模型。此外,来自所有组的相同片段进行灌注以评估通过PepT1对二肽糖基肌氨酸的摄取。我们的结果表明,对非糖尿病雌性大鼠进行胰岛素治疗可降低血糖水平,但不影响非糖尿病雄性大鼠。在雄性和雌性糖尿病大鼠中,胰岛素均不能完全降低血糖水平。胰岛素治疗可降低非糖尿病雄性大鼠的PepT1 mRNA水平,并增加非糖尿病雌性大鼠的mRNA水平,而不会影响任何性别的PepT1蛋白水平。 STZ诱发糖尿病会增加雌性大鼠的PepT1 mRNA和蛋白水平;然而,在糖尿病雄性大鼠中,mRNA水平的增加伴随着PepT1蛋白水平的下降。用胰岛素治疗糖尿病雄性大鼠可部分逆转糖尿病对PepT1 mRNA和蛋白水平的影响,而相同的治疗方法可将胰岛素治疗的糖尿病雌性大鼠中的PepT1 mRNA和蛋白完全恢复至对照水平。在非糖尿病的雄性和雌性大鼠中,胰岛素治疗对PepT1的流入速率没有影响,而STZ处理降低了转运蛋白的流入速率。用胰岛素治疗糖尿病雄性和雌性大鼠,PepT1流入率显着增加;然而,仅在糖尿病雌性大鼠中发现完全恢复。这些结果清楚地表明,胰岛素和糖尿病以性别相关的方式影响血糖水平以及PepT1活性,表达和蛋白质水平。这些结果表明,可能是雌激素的因素可能是糖尿病和胰岛素对PepT1水平和活性的性别依赖性影响的原因。

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