Effect of ipragliflozin, an SGLT2 inhibitor, on progression of diabetic microvascular complications in spontaneously diabetic Torii fatty rats

Life Sci. 2016 Feb 15:147:125-31. doi: 10.1016/j.lfs.2016.01.042. Epub 2016 Jan 29.

Abstract

Aims: We investigated the effect of the selective sodium-dependent glucose cotransporter 2 inhibitor ipragliflozin on the simultaneous progression of diabetic microvascular complications of retinopathy, nephropathy and neuropathy in individual Spontaneously Diabetic Torii (SDT) fatty rats.

Main methods: Ipragliflozin was administered to male SDT fatty rats for 12weeks. Male Sprague-Dawley rats of the same age were used as non-diabetic controls. Non-fasting plasma glucose and glycated hemoglobin levels were measured every 4weeks. Cataract formation was monitored once a week, and the electroretinogram was measured after 6weeks of treatment. After the treatment period, motor nerve conduction velocity was measured and urinalysis was conducted. Tissue samples were then dissected for histopathological examination.

Key findings: Treatment with ipragliflozin reduced glycated hemoglobin levels, inhibited the progression of cataract formation, prevented the prolongation of oscillatory potential peaks in the electroretinogram, ameliorated the slowing of motor nerve conduction velocity, and reduced the severity of glomerulosclerosis in SDT fatty rats.

Significance: These results suggest that the control of hyperglycemia with ipragliflozin slows the progression of the diabetic complications of retinopathy, nephropathy, and neuropathy.

Keywords: Cataract; Diabetic microvascular complications; Ipragliflozin L-proline (PubChem CID: 57339444); Nephropathy; Neuropathy; Retinopathy; Sodium-dependent glucose cotransporter 2; Type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetic Nephropathies / prevention & control*
  • Diabetic Neuropathies / prevention & control*
  • Diabetic Retinopathy / prevention & control*
  • Disease Progression
  • Glucosides / pharmacology*
  • Hyperglycemia / drug therapy
  • Hypoglycemic Agents / pharmacology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Thiophenes / pharmacology*

Substances

  • Glucosides
  • Hypoglycemic Agents
  • Slc5a2 protein, rat
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Thiophenes
  • ipragliflozin