Tofogliflozin, a novel sodium–glucose co‐transporter 2 inhibitor, improves renal and pancreatic function in db/db mice. (17th September 2013)

• Record Type: Journal Article
• Authors: Nagata, T; Fukuzawa, T; Takeda, M; Fukazawa, M; Mori, T; Nihei, T; Honda, K; Suzuki, Y; Kawabe, Y
• Is Part Of: British journal of pharmacology. Volume 170:Number 3(2013:Oct.)
• Page Start: 519
• Page End: 531
• Publication Date: 2013-09-17
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.12269
• Languages: English
• ISSNs: 0007-1188

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bph12269-sec-0001" sec-type="section"> <title>Background and Purpose</title> <p>Although inhibition of renal sodium–glucose co‐transporter 2 (SGLT2) has a stable glucose‐lowering effect in patients with type 2 diabetes, the effect of SGLT2 inhibition on renal dysfunction in type 2 diabetes remains to be determined. To evaluate the renoprotective effect of SGLT2 inhibition more precisely, we compared the effects of tofogliflozin (a specific SGLT2 inhibitor) with those of losartan (an angiotensin II receptor antagonist) on renal function and beta‐cell function in <italic>db/db</italic> mice.</p> </sec> <sec id="bph12269-sec-0002" sec-type="section"> <title>Experimental Approach</title> <p>The effects of 8‐week tofogliflozin or losartan treatment on renal and beta‐cell function were investigated in <italic>db/db</italic> mice by quantitative image analysis of glomerular size, mesangial matrix expansion and islet beta‐cell mass. Blood glucose, glycated Hb and insulin levels, along with urinary albumin and creatinine were measured</p> </sec> <sec id="bph12269-sec-0003" sec-type="section"> <title>Key Results</title> <p>Tofogliflozin suppressed plasma glucose and glycated Hb and preserved pancreatic beta‐cell mass and plasma insulin levels. No improvement of glycaemic conditions or insulin level was observed with losartan treatment. Although the urinary albumin/creatinine ratio of untreated <italic>db/db</italic> mice gradually increased from baseline, tofogliflozin or losartan treatment prevented this increase (by 50–70%). Tofogliflozin, but not losartan, attenuated glomerular hypertrophy. Neither tofogliflozin nor losartan altered matrix expansion.</p> </sec> <sec id="bph12269-sec-0004" sec-type="section"> <title>Conclusions and Implications</title> <p>Long‐term inhibition of renal SGLT2 by tofogliflozin not only preserved pancreatic beta‐cell function, but also prevented kidney dysfunction in a mouse model of type 2 diabetes. These findings suggest that long‐term use of tofogliflozin in patients with type 2 diabetes may prevent progression of diabetic nephropathy.</p> </sec> </abstract>