Srivastava Shivani, Pandey Harsh, Singh Surya Kumar, Tripathi Yamini Bhusan
Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, U.P, India.
Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi, U.P, India.
Adv Pharm Bull. 2019 Jun;9(2):325-330. doi: 10.15171/apb.2019.039. Epub 2019 Jun 1.
Basically insulin is known to be secreted by β cells of the pancreas. Recently, it has also been found to be produced and expressed by intestinal epithelial cells with the help of L cells secreting glucagon like peptide 1 (GLP 1). Here, we have studied the same intestinal insulin expression property in T2D rats. Following 2 weeks of high fat diet (HFD) consumption, we have been given a single dose of streptozotocin (STZ) (35 mg/kg bw). Rats were then sacrificed after 1, 7 and 21 days. The GLP 1 analogue, liraglutide was also given to one group of diabetic rats, upto their respective durations. Intestinal cells apoptosis were checked by tunnel assay, Incretin hormones secretion and dipeptidyl peptidase 4 (DPP-IV) activity were analyzed through ELISA and immunohistochemistry was used to determine the insulin expression of intestine at different time interval during diabetes progression. As compared to 1 and 21 days, we have found minor cells apoptosis in 7 days group along with high level of GLP 1 in diabetic model. Further, these effects were enhanced by liraglutide. In response to these we have found, decreased insulin expression after 21 days and with no significant effect upto 7 days in diabetic control groups. In contrast to this, GLP-1 level and insulin expression enhances prominently after 7 days of liraglutide treatment. These results explain the self-adapting approach of intestinal cells against diabetes onset and insulin expression enhancing property of liraglutide under stressful conditions. This study should be continued in future for the development of intestinal insulin producing drugs, to control diabetes under irreversible β cells damage.
基本上，胰岛素是由胰腺的β细胞分泌的。最近，人们还发现它在分泌胰高血糖素样肽1（GLP - 1）的L细胞的帮助下，由肠道上皮细胞产生和表达。在此，我们研究了2型糖尿病大鼠中相同的肠道胰岛素表达特性。在食用高脂肪饮食（HFD）2周后，我们给大鼠单次注射链脲佐菌素（STZ）（35 mg/kg体重）。然后在1、7和21天后处死大鼠。一组糖尿病大鼠还被给予GLP - 1类似物利拉鲁肽，持续相应的时间。通过隧道试验检查肠道细胞凋亡，通过酶联免疫吸附测定（ELISA）分析肠促胰岛素激素分泌和二肽基肽酶4（DPP - IV）活性，并使用免疫组织化学来确定糖尿病进展过程中不同时间间隔肠道的胰岛素表达。与1天和21天相比，我们发现在7天组中细胞凋亡较少，并且糖尿病模型中GLP - 1水平较高。此外，利拉鲁肽增强了这些作用。针对我们所发现的这些情况，我们发现在糖尿病对照组中，21天后胰岛素表达下降，而在7天内无显著影响。与此相反，利拉鲁肽治疗7天后，GLP - 1水平和胰岛素表达显著增强。这些结果解释了肠道细胞针对糖尿病发作的自我适应方法以及利拉鲁肽在应激条件下增强胰岛素表达的特性。为了开发肠道产生胰岛素的药物以在不可逆的β细胞损伤情况下控制糖尿病，这项研究未来应该继续进行。
