Comprehensive renoprotective effects of ipragliflozin on early diabetic nephropathy in mice

Area of Science:

• Nephrology
• Endocrinology
• Pharmacology

Background:

• Diabetic kidney disease (DKD) is a major complication of diabetes.
• Sodium glucose co-transporter 2 inhibitors (SGLT2i) show promise in preventing DKD progression.
• The precise molecular mechanisms of SGLT2i in DKD require further elucidation.

Purpose of the Study:

• To investigate the dose-dependent pharmacological effects of ipragliflozin on molecular mechanisms in diabetic nephropathy.
• To assess the impact of ipragliflozin on renal hypertrophy, oxidative stress, hypoxia, and podocyte integrity.

Main Methods:

• Administration of varying doses of ipragliflozin to type 2 and type 1 diabetic mice.
• Measurement of blood glucose, urinary albumin excretion, renal/glomerular hypertrophy, NADPH oxidase 4 expression, oxidative stress markers, and renal cortical oxygen tension.
• Glomeruli isolation for detailed podocyte analysis.

Main Results:

• High-dose ipragliflozin lowered blood glucose and reduced albuminuria in type 2 diabetic mice.
• Both high and low doses of ipragliflozin inhibited renal/glomerular hypertrophy and decreased oxidative stress.
• Ipragliflozin preserved podocyte integrity, reduced renal cortical hypoxia, and improved oxygen tension.
• Ipragliflozin reduced albuminuria in both type 1 and type 2 diabetic models.

Conclusions:

• Ipragliflozin demonstrates dose-dependent renoprotective effects in early diabetic nephropathy.
• Low-dose ipragliflozin effectively reduces renal cortical hypoxia and abnormal hemodynamics.
• High-dose ipragliflozin provides additional benefits by mitigating oxidative stress in tubular and glomerular cells.