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Albert Salehi

S Albert Salehi

Research team manager

Albert Salehi

Reduced Expression of Chl1 gene Impairs Insulin Secretion by Down-Regulating the Expression of Key Molecules of β-cell Function

Author

  • Jalal Taneera
  • Sarah Dhaiban
  • Mahmood Hachim
  • Abdul Khader Mohammed
  • Debasmita Mukhopadhyay
  • Khuloud Bajbouj
  • Rifat Hamoudi
  • Albert Salehi
  • Mawieh Hamad

Summary, in English

Silencing of Chl1 gene expression has been previously reported to reduce insulin secretion. Nevertheless, the mechanism underlying this effect remains unclear. In this study, we performed a serial of studies to investigate how Chl1 affects insulin secretion in INS-1 cells. RNA-sequencing was used to investigate the expression of CHL1 in human adipose, liver, muscle, and human islets. Silencing of Chl1 in INS-1 cells was done to assess its impact on the insulin secretion, content, cell viability, and apoptosis. In addition, gene set enrichment analysis (GSEA) was performed to identify possible molecular signatures that associate with Chl1 expression silencing. RNA sequencing data revealed a high expression of CHL1 in pancreatic islets and adipose tissues compared to liver and muscles tissues. Diabetic islets exhibited a lower expression of CHL1 as compared to non-diabetic islets. CHL1 expression was found to correlate positively with insulin secretory index, GLP1R but inversely with HbA 1cand BMI. Silencing of Chl1 in INS-1 cells markedly reduced insulin content and secretion. The expression of key molecules of β-cell function including Insulin, Pdx1, Gck, Glut2, and Insrβ was down-regulated in Chl1 -silenced cells at transcriptional and translational levels. Cell viability, apoptosis, and proliferation rate were not affected. GSEA showed that the insulin-signaling pathway was influenced in Chl1 -silenced cells. Silencing of Chl1 impairs β-cell function by disrupting the activity of key signaling pathways of importance for insulin biosynthesis and secretion.

Department/s

  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Islet cell physiology

Publishing year

2021

Language

English

Pages

864-872

Publication/Series

Experimental and Clinical Endocrinology and Diabetes

Volume

129

Issue

12

Document type

Journal article

Publisher

Georg Thieme Verlag

Topic

  • Endocrinology and Diabetes

Keywords

  • Chl1
  • diabetes
  • gene expression microarray
  • GSEA.
  • human islets
  • INS-1 (832/31)
  • insulin secretion

Status

Published

Research group

  • Islet cell physiology

ISBN/ISSN/Other

  • ISSN: 0947-7349