SGLT1/2 inhibition improves glycemic control and multi-organ protection in type 1 diabetes

Lakshini Yasaswi Herat; Jennifer Rose Matthews; Moira Hibbs; Elizabeth Piroska Rakoczy; Markus Peter Schlaich; Vance Bruce Matthews

doi:10.1016/j.isci.2023.107260

SGLT1/2 inhibition improves glycemic control and multi-organ protection in type 1 diabetes

iScience. 2023 Jul 3;26(8):107260. doi: 10.1016/j.isci.2023.107260. eCollection 2023 Aug 18.

Authors

Lakshini Yasaswi Herat¹, Jennifer Rose Matthews¹, Moira Hibbs², Elizabeth Piroska Rakoczy³, Markus Peter Schlaich^{4

5}, Vance Bruce Matthews¹

Affiliations

¹ 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.
² Research Centre, Royal Perth Hospital, Perth, WA 6000, Australia.
³ Department of Molecular Ophthalmology, University of Western Australia, Crawley, WA 6009, Australia.
⁴ Dobney Hypertension Centre, Medical School - Royal Perth Hospital Unit / Royal Perth Hospital Medical Research Foundation, University of Western Australia, Crawley, WA 6009, Australia.
⁵ Department of Cardiology and Department of Nephrology, Royal Perth Hospital, Perth, WA 6000, Australia.

Abstract

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.

Keywords: Cell biology; Human metabolism.