Herat Lakshini Yasaswi, Matthews Jennifer Rose, Hibbs Moira, Rakoczy Elizabeth Piroska, Schlaich Markus Peter, Matthews Vance Bruce
Dobney Hypertension Centre, School of Biomedical Sciences - Royal Perth Hospital Unit / Royal Perth Hospital Medical Research Foundation, University of Western Australia, Crawley, WA 6009, Australia.
Research Centre, Royal Perth Hospital, Perth, WA 6000, Australia.
iScience. 2023 Jul 3;26(8):107260. doi: 10.1016/j.isci.2023.107260. eCollection 2023 Aug 18.
Sodium glucose cotransporters (SGLTs) are transport proteins that are expressed throughout the body. Inhibition of SGLTs is a relatively novel therapeutic strategy to improve glycemic control and has been shown to promote cardiorenal benefits. Dual SGLT1/2 inhibitors (SGLT1/2i) such as sotagliflozin target both SGLT1 and 2 proteins. Sotagliflozin or vehicle was administered to diabetic Akimba mice for 8 weeks at a dose of 25 mg/kg/day. Urine glucose levels, water consumption, and body weight were measured weekly. Serum, kidney, pancreas, and brain tissue were harvested under terminal anesthesia. Tissues were assessed using immunohistochemistry or ELISA techniques. Treatment with sotagliflozin promoted multiple metabolic benefits in diabetic Akimba mice resulting in decreased blood glucose and improved polydipsia. Sotagliflozin also prevented mortalities associated with diabetes. Our data suggests that there is the possibility that combined SGLT1/2i may be superior to SGLT2i in controlling glucose homeostasis and provides protection of multiple organs affected by diabetes.
钠葡萄糖协同转运蛋白（SGLTs）是在全身表达的转运蛋白。抑制SGLTs是一种相对新颖的改善血糖控制的治疗策略，并且已显示出对心肾有益。双重SGLT1/2抑制剂（SGLT1/2i），如索格列净，作用于SGLT1和2两种蛋白。将索格列净或赋形剂以25mg/kg/天的剂量给予糖尿病Akimba小鼠，持续8周。每周测量尿葡萄糖水平、水消耗量和体重。在终末麻醉下采集血清、肾脏、胰腺和脑组织。使用免疫组织化学或ELISA技术评估组织。索格列净治疗在糖尿病Akimba小鼠中促进了多种代谢益处，导致血糖降低和烦渴改善。索格列净还预防了与糖尿病相关的死亡。我们的数据表明，联合使用SGLT1/2i在控制葡萄糖稳态方面可能优于SGLT2i，并能为受糖尿病影响的多个器官提供保护。
