C-peptide and islet transplantation improve glomerular filtration barrier in diabetic nephropathy rats

Transpl Immunol. 2020 Oct:62:101322. doi: 10.1016/j.trim.2020.101322. Epub 2020 Aug 13.

Abstract

Objectives: Islet transplantation has been proved to be effective in delaying early stage of DN. This study was established to observe the mechanism of islet transplantation on early diabetic nephropathy (DN).

Method: The diabetes mellitus (DM) rat model was established by an injection of a single-dose streptozotocin. According to the treatment, the rats were randomly divided into 4 groups: the untreated DN rats (DN group); the C-peptide treated rats (CP group); the islet transplanted rats (IT group); the normal control rats (NC group). Renal function and structure of glomerular filtration barrier (GFB) were evaluated by urinalysis and histopathological examination, respectively. The renal fibrotic factors, TGF- β1 and CTGF, as well as the anti-renal fibrosis factor HGF were assessed by immunohistochemical staining and western blotting methods.

Results: After C-peptide treatment and islet transplantation, the GFB structure was obviously improved. The blood glucose significantly decreased in the IT group. The 24h urine protein and glomerular basement membrane thickness decreased, the pathological changes of podocytes improved, TGF- β1 and CTGF decreased and HGF increased in the CP group and the IT group compared with that in the DN group (P < 0.05), especially in the IT group.

Conclusion: Islet transplantation could ameliorate the structure of GFB of early DN in a rat model, and the treatment effect was partly attributed to the restoration of C-peptide concentration. Suppressing the fibrosis system can be the potential mechanism of islet transplantation, which is independent of blood glucose control.

Keywords: C-peptide; Islet transplantation; diabetes mellitus; diabetic nephropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • C-Peptide / metabolism*
  • Diabetes Mellitus / therapy*
  • Diabetic Nephropathies / therapy*
  • Disease Models, Animal
  • Fibrosis
  • Glomerular Filtration Barrier / metabolism*
  • Glomerular Filtration Barrier / pathology*
  • Humans
  • Islets of Langerhans Transplantation*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin
  • Transforming Growth Factor beta1 / metabolism
  • Urinalysis

Substances

  • C-Peptide
  • Transforming Growth Factor beta1
  • Streptozocin