Silk Fibroin Promotes the Regeneration of Pancreatic β-Cells in the C57BL/KsJ- Leprdb/db Mouse

Molecules. 2020 Jul 17;25(14):3259. doi: 10.3390/molecules25143259.

Abstract

Diabetes mellitus is a chronic metabolic disease, and its progression leads to serious complications. Although various novel therapeutic approaches for diabetes mellitus have developed in the last three decades, its prevalence has been rising more rapidly worldwide. Silk-related materials have been used as anti-diabetic remedies in Oriental medicine and many studies have shown the effects of silk fibroin (SF) in both in vitro and in vivo models. In our previous works, we reported that hydrolyzed SF improved the survival of HIT-T15 cells under high glucose conditions and ameliorated diabetic dyslipidemia in a mouse model. However, we could not provide a precise molecular mechanism. To further evaluate the functions of hydrolyzed SF on the pancreatic β-cell, we investigated the effects of hydrolyzed SF on the pancreatic β-cell proliferation and regeneration in the mouse model. Hydrolyzed SF induced the expression of the proliferating cell nuclear antigen (PCNA) and reduced the apoptotic cell population in the pancreatic islets. Hydrolyzed SF treatment not only induced the expression of transcription factors involved in the pancreatic β-cell regeneration in RT-PCR results but also increased neurogenin3 and Neuro D protein levels in the pancreas of those in the group treated with hydrolyzed SF. In line with this, hydrolyzed SF treatment generated insulin mRNA expressing small cell colonies in the pancreas. Therefore, our results suggest that the administration of hydrolyzed SF increases the pancreatic β-cell proliferation and regeneration in C57BL/KsJ-Leprdb/db mice.

Keywords: diabetes mellitus; diabetic mice; insulin; silk fibroin; β-cell.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Cell Proliferation / drug effects
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / pathology
  • Fibroins / chemistry
  • Fibroins / pharmacology*
  • Gene Expression Regulation / drug effects
  • Humans
  • Insulin-Secreting Cells / drug effects
  • Medicine, East Asian Traditional
  • Mice
  • Mice, Inbred NOD
  • Nerve Tissue Proteins / genetics*
  • Pancreas / drug effects
  • Pancreas / pathology
  • Proliferating Cell Nuclear Antigen / genetics*
  • Regeneration / drug effects

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Nerve Tissue Proteins
  • Neurog3 protein, mouse
  • Proliferating Cell Nuclear Antigen
  • Fibroins