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Reduced Expression of Chl1 gene Impairs Insulin Secretion by Down-Regulating the Expression of Key Molecules of
Jalal Taneera1, Sarah Dhaiban1, Mahmood Hachim1
1Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates.
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.
Insights
Silencing the Chl1 gene impairs pancreatic beta-cell function by reducing insulin secretion and content. This disruption affects key molecules involved in insulin biosynthesis and signaling pathways.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Chl1 gene expression silencing reduces insulin secretion, but the mechanism is unclear.
- CHL1 is highly expressed in pancreatic islets and adipose tissues.
- Diabetic islets show lower CHL1 expression compared to non-diabetic islets.
Purpose of the Study:
- Investigate the mechanism by which Chl1 affects insulin secretion in INS-1 cells.
- Assess the impact of Chl1 silencing on insulin secretion, content, cell viability, and apoptosis.
- Identify molecular signatures associated with Chl1 expression silencing using gene set enrichment analysis (GSEA).
Main Methods:
- RNA-sequencing to analyze CHL1 expression in human tissues and INS-1 cells.
- Silencing of Chl1 in INS-1 cells.
- Measurement of insulin secretion and content.
- Assessment of cell viability, apoptosis, and proliferation.
- Gene set enrichment analysis (GSEA).
Main Results:
- CHL1 expression is high in islets and adipose tissue, inversely correlated with HbA1c and BMI.
- Silencing Chl1 in INS-1 cells significantly reduced insulin content and secretion.
- Key beta-cell function molecules (Insulin, Pdx1, Gck, Glut2, Insrβ) were downregulated.
- Cell viability, apoptosis, and proliferation remained unaffected.
- GSEA indicated that the insulin-signaling pathway was influenced by Chl1 silencing.
Conclusions:
- Chl1 silencing impairs pancreatic beta-cell function by disrupting insulin biosynthesis and secretion.
- The study identifies Chl1 as a crucial factor in maintaining beta-cell function.
- Chl1 plays a significant role in regulating insulin signaling pathways.
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