TY - JOUR
T1 - SGLT1/2 inhibition improves glycemic control and multi-organ protection in type 1 diabetes
AU - Herat, Lakshini Yasaswi
AU - Matthews, Jennifer Rose
AU - Hibbs, Moira
AU - Rakoczy, Elizabeth Piroska
AU - Schlaich, Markus Peter
AU - Matthews, Vance Bruce
PY - 2023/8/18
Y1 - 2023/8/18
N2 - 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.
AB - 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.
KW - Cell biology
KW - Human metabolism
UR - http://www.scopus.com/inward/record.url?scp=85165009976&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2023.107260
DO - 10.1016/j.isci.2023.107260
M3 - Article
C2 - 37520739
AN - SCOPUS:85165009976
SN - 2589-0042
VL - 26
JO - Iscience
JF - Iscience
IS - 8
M1 - 107260
ER -