Abstract
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 HbA1c
and 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.
Key words
diabetes - insulin secretion -
Chl1
- INS-1 (832/31) - gene expression microarray - human islets - GSEA.