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A Novel Indoline Derivative Ameliorates Diabesity-Induced Chronic Kidney Disease by Reducing Metabolic Abnormalities

Anna Permyakova1, Asaad Gammal1, Liad Hinden1

  • 1Faculty of Medicine, School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.

Frontiers in Endocrinology
|March 29, 2020
PubMed

Insights

Novel compound AN1284 shows promise in treating diabetic kidney disease. This indoline derivative improved kidney function and metabolic health in obese diabetic mice, offering potential for human diabesity patients.

Area of Science:

  • Nephrology
  • Endocrinology
  • Metabolic Diseases

Background:

  • Diabetes and obesity, collectively termed diabesity, are major drivers of chronic kidney disease (CKD).
  • Effective therapeutic strategies to halt or reverse diabetic kidney disease progression are urgently needed.

Purpose of the Study:

  • To investigate the therapeutic potential of a novel indoline derivative, AN1284, in a mouse model of type 2 diabetes with obesity.
  • To assess AN1284's effects on kidney function, metabolic parameters, and organ health.

Main Methods:

  • Six-week-old BKS Cg-Dock 7m+/+ Leprdb/J mice (a model for type 2 diabetes and obesity) were treated with AN1284 (2.5 or 5 mg/kg/day) for 3 months via implanted micro-osmotic pumps.
  • Evaluations included renal, pancreatic, and liver assessments, alongside measurements of energy utilization.

Main Results:

  • AN1284 treatment significantly improved kidney function by reducing urinary albumin and creatinine levels.
  • The compound prevented renal inflammation and morphological damage, while also promoting weight loss and reducing body fat mass.
  • AN1284 preserved insulin sensitivity, maintained pancreatic beta cell mass, and ameliorated dyslipidemia, hepatic steatosis, and liver injury.

Conclusions:

  • AN1284, an indoline derivative, demonstrates significant renoprotective effects in a preclinical model of diabesity.
  • By ameliorating metabolic abnormalities associated with hyperglycemia, AN1284 offers potential therapeutic benefits for preventing chronic kidney disease in human subjects with diabesity.
Keywords:
chronic kidney diseasediabetesfatty liverindoline derivativeinsulin resistanceobesity

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