Deletion of Bmal1 Impairs Pancreatic β-Cell Function via Mitochondrial Signaling Pathway

Abstract EN

Several studies have demonstrated that brain and muscle Arnt-like protein-1 (Bmal1) acts as a core clock gene for maintaining normal cell function, including hepatocytes and cardiomyocytes.

Loss of Bmal1 is associated with type 2 diabetes due to pancreatic β-cell failure.

However, little information is available about its role and mechanism in pancreatic β-cell.

To address this, we investigated the consequences of Bmal1 inhibition in an insulinoma cell line (INS-1) by using small interfering RNA (siRNA).

We observed that knockout of Bmal1 impaired glucose-stimulated insulin secretion in β-cell.

Meanwhile, the depletion of Bmal1 in β-cell caused an adverse change in mitochondrial membrane potential and mitochondrial architecture.

Deletion of Bmal1 attenuated mRNA and protein expression of mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2) and enhanced the expression of fission 1 (Fis1).

In summary, the deletion of Bmal1 impaired β-cell function may be via the mitochondrial signaling pathway in INS-1 cells.