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

Taneera, Jalal LU ; Dhaiban, Sarah ; Hachim, Mahmood ; Mohammed, Abdul Khader ; Mukhopadhyay, Debasmita ; Bajbouj, Khuloud ; Hamoudi, Rifat ; Salehi, Albert LU orcid and Hamad, Mawieh (2021) In Experimental and Clinical Endocrinology and Diabetes 129(12). p.864-872
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... (More)

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.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Chl1, diabetes, gene expression microarray, GSEA., human islets, INS-1 (832/31), insulin secretion
in
Experimental and Clinical Endocrinology and Diabetes
volume
129
issue
12
pages
9 pages
publisher
Georg Thieme Verlag
external identifiers
  • pmid:31614370
  • scopus:85121231003
ISSN
0947-7349
DOI
10.1055/a-1014-2544
language
English
LU publication?
yes
id
e519bdec-2c82-4f1f-9430-1e96e41716fe
date added to LUP
2022-01-27 12:04:26
date last changed
2024-06-16 00:36:43
@article{e519bdec-2c82-4f1f-9430-1e96e41716fe,
  abstract     = {{<p>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 <sub>1c</sub>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.</p>}},
  author       = {{Taneera, Jalal and Dhaiban, Sarah and Hachim, Mahmood and Mohammed, Abdul Khader and Mukhopadhyay, Debasmita and Bajbouj, Khuloud and Hamoudi, Rifat and Salehi, Albert and Hamad, Mawieh}},
  issn         = {{0947-7349}},
  keywords     = {{Chl1; diabetes; gene expression microarray; GSEA.; human islets; INS-1 (832/31); insulin secretion}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{864--872}},
  publisher    = {{Georg Thieme Verlag}},
  series       = {{Experimental and Clinical Endocrinology and Diabetes}},
  title        = {{Reduced Expression of Chl1 gene Impairs Insulin Secretion by Down-Regulating the Expression of Key Molecules of β-cell Function}},
  url          = {{http://dx.doi.org/10.1055/a-1014-2544}},
  doi          = {{10.1055/a-1014-2544}},
  volume       = {{129}},
  year         = {{2021}},
}