TY - JOUR
T1 - Roles of Sodium-Glucose Cotransporter 2 of Mesangial Cells in Diabetic Kidney Disease
AU - Wakisaka, Masanori
AU - Nakamura, Kuniyuki
AU - Nakano, Toshiaki
AU - Kitazono, Takanari
N1 - Publisher Copyright:
© 2021 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2021/8/1
Y1 - 2021/8/1
N2 - We have been studying the presence of sodium-glucose cotransporter 2 (SGLT2) in mesangial cells and pericytes since 1992. Recent large placebo-controlled studies of SGLT2 inhibitors in patients with type 2 diabetes mellitus have reported desirable effects of the inhibitors on the diabetic kidney and the diabetic heart. Most studies have indicated that these effects of SGLT2 inhibitors could be mediated by the tubuloglomerular feedback system. However, a recent study about urine sodium excretion in the presence of an SGLT2 inhibitor did not show any increases in urine sodium excretion. A very small dose of an SGLT2 inhibitor did not inhibit SGLT2 at the S1 segment of proximal tubules. Moreover, SGLT2 inhibition protects against progression in chronic kidney disease with and without type 2 diabetes. In these circumstances, the tubuloglomerular feedback hypothesis involves several theoretical concerns that must be clarified. The presence of SGLT2 in mesangial cells seems to be very important for diabetic nephropathy. We now propose a novel mechanism by which the desirable effects of SGLT2 inhibitors on diabetic nephropathy are derived from the direct effect on SGLT2 expressed in mesangial cells.
AB - We have been studying the presence of sodium-glucose cotransporter 2 (SGLT2) in mesangial cells and pericytes since 1992. Recent large placebo-controlled studies of SGLT2 inhibitors in patients with type 2 diabetes mellitus have reported desirable effects of the inhibitors on the diabetic kidney and the diabetic heart. Most studies have indicated that these effects of SGLT2 inhibitors could be mediated by the tubuloglomerular feedback system. However, a recent study about urine sodium excretion in the presence of an SGLT2 inhibitor did not show any increases in urine sodium excretion. A very small dose of an SGLT2 inhibitor did not inhibit SGLT2 at the S1 segment of proximal tubules. Moreover, SGLT2 inhibition protects against progression in chronic kidney disease with and without type 2 diabetes. In these circumstances, the tubuloglomerular feedback hypothesis involves several theoretical concerns that must be clarified. The presence of SGLT2 in mesangial cells seems to be very important for diabetic nephropathy. We now propose a novel mechanism by which the desirable effects of SGLT2 inhibitors on diabetic nephropathy are derived from the direct effect on SGLT2 expressed in mesangial cells.
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U2 - 10.1210/jendso/bvab083
DO - 10.1210/jendso/bvab083
M3 - Review article
AN - SCOPUS:85111937675
VL - 5
JO - Journal of the Endocrine Society
JF - Journal of the Endocrine Society
SN - 2472-1972
IS - 8
M1 - bvab083
ER -