Inhibition of notch signalling and mesangial expansion by combined glucagon like peptide-1 agonist and crocin therapy in animal model of diabetic nephropathy

Arch Physiol Biochem. 2023 Apr;129(2):544-554. doi: 10.1080/13813455.2020.1846203. Epub 2020 Dec 7.

Abstract

Diabetic nephropathy (DN) is one of the devastating complications in diabetes mellitus (DM). Glucagon-like peptide-1 (GLP-1) is one of the incretins secreted from L cells in the intestine. Crocin (a carotenoid component of saffron) has antioxidants properties. We investigated the renal effects of Exendin-4 as a GLP-1 agonist and Crocin in DN.Thirty male rats were divided into five groups: control, type II DM, type II DM + Exendin-4, type II DM + Crocin ‏ and type II DM + Exendine-4 + Crocin. At the end of the experimental period, systolic and diastolic blood pressures were measured, and GFR was calculated. Blood and urine samples were collected for biochemical analysis. Tissue samples were collected from the kidney for histological examination and biochemical measurements of protein expression.Treatment with GLP-1 agonist or Crocin caused a significant improvement in renal function. Better results were achieved with simultaneous administration of both drugs with inhibition of notch signalling pathway and the related proteins.

Keywords: Crocin; Diabetic nephropathy; GLP-1 agonist; notch signalling; saffron.

MeSH terms

  • Animals
  • Carotenoids / pharmacology
  • Carotenoids / therapeutic use
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Experimental* / metabolism
  • Diabetic Nephropathies* / metabolism
  • Exenatide / pharmacology
  • Exenatide / therapeutic use
  • Glucagon-Like Peptide 1
  • Male
  • Models, Animal
  • Rats

Substances

  • Glucagon-Like Peptide 1
  • crocin
  • Exenatide
  • Carotenoids

Supplementary concepts

  • Diabetes Mellitus, Noninsulin-Dependent, Type 4