Biomaterial Database

Comprehensive renoprotective effects of ipragliflozin on early diabetic nephropathy in mice. 2018

Michitsugu Kamezaki, and Tetsuro Kusaba, and Kazumi Komaki, and Yohei Fushimura, and Noriko Watanabe, and Kisho Ikeda, and Takashi Kitani, and Noriyuki Yamashita, and Masahiro Uehara, and Yuhei Kirita, and Yayoi Shiotsu, and Ryosuke Sakai, and Takuya Fukuda, and Masahiro Yamazaki, and Michiaki Fukui, and Satoaki Matoba, and Keiichi Tamagaki

Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Clinical and experimental studies have shown that sodium glucose co-transporter 2 inhibitors (SGLT2i) contribute to the prevention of diabetic kidney disease progression. In order to clarify its pharmacological effects on the molecular mechanisms underlying the development of diabetic kidney disease, we administered different doses of the SGLT2i, ipragliflozin, to type 2 diabetic mice. A high-dose ipragliflozin treatment for 8 weeks lowered blood glucose levels and reduced urinary albumin excretion. High- and low-dose ipragliflozin both inhibited renal and glomerular hypertrophy, and reduced NADPH oxidase 4 expression and subsequent oxidative stress. Analysis of glomerular phenotypes using glomeruli isolation demonstrated that ipragliflozin preserved podocyte integrity and reduced oxidative stress. Regarding renal tissue hypoxia, a short-term ipragliflozin treatment improved oxygen tension in the kidney cortex, in which SGLT2 is predominantly expressed. We then administered ipragliflozin to type 1 diabetic mice and found that high- and low-dose ipragliflozin both reduced urinary albumin excretion. In conclusion, we confirmed dose-dependent differences in the effects of ipragliflozin on early diabetic nephropathy in vivo. Even low-dose ipragliflozin reduced renal cortical hypoxia and abnormal hemodynamics in early diabetic nephropathy. In addition to these effects, high-dose ipragliflozin exerted renoprotective effects by reducing oxidative stress in tubular epithelia and glomerular podocytes.

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D008297	Male		Males
D008807	Mice, Inbred BALB C	An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research.	BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D005960	Glucosides	A GLYCOSIDE that is derived from GLUCOSE.	Glucoside
D000077203	Sodium-Glucose Transporter 2 Inhibitors	Compounds that inhibit SODIUM-GLUCOSE TRANSPORTER 2. They lower blood sugar by preventing the reabsorption of glucose by the kidney and are used in the treatment of TYPE 2 DIABETES MELLITUS.	Gliflozin,SGLT-2 Inhibitor,SGLT2 Inhibitor,Sodium-Glucose Transporter 2 Inhibitor,Gliflozins,SGLT-2 Inhibitors,SGLT2 Inhibitors,Inhibitor, SGLT-2,Inhibitor, SGLT2,SGLT 2 Inhibitor,SGLT 2 Inhibitors,Sodium Glucose Transporter 2 Inhibitor,Sodium Glucose Transporter 2 Inhibitors
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013876	Thiophenes	A monocyclic heteroarene furan in which the oxygen atom is replaced by a sulfur.	Thiophene
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus