Overexpression of Gjb4 impairs cell proliferation and insulin secretion in primary islets cells

Background:

As altered gene expression contributes to the development of Type- 2 diabetes (T2D), the analysis of differentially expressed genes between diabetes susceptible and diabetes resistant mouse models is an important tool for the determination of putative candidate genes which participate in the pathology. RNA-seq and array data comparing pancreatic gene expression of New Zealand obese (NZO) mice developing diabetes with diabetes-resistant B6.V-ob/ob (ob/ob) mice proposed Gap junction beta-4 protein (Gjb4) as a potential new T2D candidate gene.

Methods:

Gjb4 was virally overexpressed in INS-1 cells and in primary islet cells derived from standard B6 mice. A BrdU incorporation assay was performed in order to determine the proliferation rate of these cells. Alterations in the insulin secretion capacity were assessed with a glucose-stimulated insulin secretion test. INS-1 cell apoptosis rate was determined by Western blotting assessing cleaved caspase 3 levels.

Results:

Overexpression of Gjb4 in primary islet cells significantly reduced their proliferation (-47%) and insulin secretion (-38%). Moreover, the INS-1 cells overexpressing Gjb4 displayed higher rates of apoptosis.

Conclusion:

The gap junction protein Gjb4, which is highly expressed in NZO islets, plays an important role in the development of T2D by altering islet-cells function, inducing apoptosis and inhibiting proliferation.