Abstract: FR-PO594

PBI-4547, a Novel Anti-Diabetic Agent, Prevents Diabetic Nephropathy and Protects β-Cells in NOD Mice, a Model of Type 1 Diabetes

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Gagnon, Lyne, Prometic BioSciences Inc., Laval, Quebec, Canada
  • Hince, Kathy, Prometic BioSciences Inc., Laval, Quebec, Canada
  • Sarra-Bournet, François, Prometic BioSciences Inc., Laval, Quebec, Canada
  • Tremblay, Mikaël, Prometic BioSciences Inc., Laval, Quebec, Canada
  • Cloutier, Marie-Pier, Prometic BioSciences Inc., Laval, Quebec, Canada
  • Létourneau, Sylvie, Prometic BioSciences Inc., Laval, Quebec, Canada
  • Laurin, Pierre, Prometic BioSciences Inc., Laval, Quebec, Canada
  • Grouix, Brigitte, Prometic BioSciences Inc., Laval, Quebec, Canada
  • Leblond, Francois A., Prometic BioSciences Inc., Laval, Quebec, Canada
Background

Kidney disease is a cause of substantial morbidity and mortality in type 1 diabetes (T1D). Up to 40% of patients with T1D develop macroalbuminuria, and up to 75% of these patients progress to end-stage renal disease (ESRD) within 10 years. PBI-4547 is a novel first-in-class orally active antidiabetic compound which displays pleiotropic activities and has been shown to reduce NASH, diabetes and fibrosis of kidney in different animal models. In the present study, we examined whether PBI-4547 may prevent diabetic nephropathy in NOD mice, a model of type 1 diabetes.

Methods

NOD/ShiLtJ female mice (8 weeks of age) received vehicle (water) or PBI-4547 (10 and 25 mg/kg/day) by daily gastric gavage for 23 weeks.

Results

In kidney, PBI-4547 protects against lesions by reducing glomerular volume and mesangial cross sectional area. Furthermore, tubular lesions were absent in PBI-4547-treated mice. Tubular dystrophy as PAS granular accumulation was constantly present in proximal tubules of NOD control mice and was completely abrogated by treatment with PBI-4547. Mice treated with PBI-4547 did not develop diabetes. OGTT was also normalized in PBI-4547-treated mice. PBI-4547 partially prevented islets destruction, which contributed to maintain normoglycemia.

Conclusion

This data suggests that PBI-4547 prevents diabetic nephropathy and complete destruction of β-cells and islets in type 1 diabetes model.

Funding

  • Commercial Support