Sotagliflozin Promotes Anti-oxidant Properties in the Kidneys of Type 1 Diabetic Akimba Mice
Abstract
Diabetes Mellitus (DM) is a chronic metabolic disease consisting of Type 1 or Type 2 diabetes. Although treatment of Type 1 diabetes primarily involves insulin therapy, inhibitors of sodium glucose co-transporters (SGLT’s) are a promising new therapeutic. Of particular interest are the two family members, SGLT1 and SGLT2 that collectively contribute to 100% of filtered glucose reabsorption within the kidneys. Consequently, sole SGLT2 inhibitors (SGLT2i) and dual SGLT1/2 inhibitors (SGLT1/2i) contribute to reducing blood glucose levels by reducing glucose reabsorption and promoting glucosuria and natriuresis. Research from our team on SGLT2i, showed that there is a compensatory mechanism whereby SGLT1 is upregulated. This therefore may warrant the combined use of SGLT1/2i. Our in vitro results demonstrated that whilst both the sole SGLT2i empagliflozin (EMPA) and dual SGLT1/2i sotagliflozin (SOTAG) significantly reduce glucose uptake within HK2 cells, the latter was more effective. In addition, our in vitro results indicate significantly more pronounced upregulation of SGLT1 protein with EMPA compared to SOTAG. Our in vivo mechanistic findings demonstrated that SGLT1/2i significantly increased renal SOD1 levels, whilst SGLT2i significantly elevated renal SOD2 levels. Therefore, our study highlighted that SGLT2i and SGLT1/2i differentially regulate protective anti-oxidant proteins in the kidney.
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