Renal protective effect of pinitol in experimental diabetes

Eur J Pharmacol. 2020 Aug 5:880:173130. doi: 10.1016/j.ejphar.2020.173130. Epub 2020 Apr 30.

Abstract

Pinitol is a natural antidiabetic agent shown to prevent or ameliorate metabolic and overall vascular and neural function. In the present study we have evaluated the potential benefits of pinitol on renal function of streptozotocin (STZ)-induced diabetic rats. Both euglycemic or 8-week or 16-week diabetic rats were treated with either saline (1 ml/kg/12h; p.o) or pinitol (20 mg/kg/12h; p.o). The renal function was evaluated by using metabolic cages, renal hemodynamic and tubular parameters measurements. Histological examination and evaluation of the protein expression of renal markers such as nephrin, TGFβ and pERK were also performed. Pinitol decreased by 50% the increased urinary albumin/creatinine ratio in both 8-week and 16 week diabetic rats. In addition, the glomerular volume of 16-week rats increased by 55% and this increase was blunted by pinitol. Remarkably, pressure-natriuresis was completely blunted in both 8 and 16-week diabetic rats but this impairment was prevented by pinitol in both treatment regimens. Pinitol ameliorated renal lesions and also prevented the decrease in nephrin expression and the increase of pERK and TGFβ expression in both diabetic groups. Natriuresis due to high renal perfusion pressure increased 7-fold in control animals but was blocked in 16-week diabetic rats and remarkably pinitol partially restored pressure natriuresis (3-fold increase in sodium excretion during pressure natriuresis). Pinitol prevents and ameliorates albuminuria, glomerular expansion, impairment of pressure-natriuresis, renal structural alterations and changes of renal markers and has the potential to be tested for the prevention of diabetic kidney disease.

Keywords: Diabetic kidney disease; Glomerulopathy; Inositols; Insulin mimetics; Pressure natriuresis; Renoprotection.

MeSH terms

  • Albuminuria / drug therapy
  • Albuminuria / metabolism
  • Albuminuria / pathology
  • Albuminuria / physiopathology
  • Animals
  • Creatinine / urine
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Hemodynamics
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Inositol / analogs & derivatives*
  • Inositol / pharmacology
  • Inositol / therapeutic use
  • Kidney / drug effects*
  • Kidney / pathology
  • Kidney / physiology
  • Male
  • Membrane Proteins / metabolism
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Rats, Wistar
  • Transforming Growth Factor beta / metabolism

Substances

  • Hypoglycemic Agents
  • Membrane Proteins
  • Protective Agents
  • Transforming Growth Factor beta
  • nephrin
  • pinitol
  • Inositol
  • Creatinine
  • Extracellular Signal-Regulated MAP Kinases