Drp1 Overexpression Decreases Insulin Content in Pancreatic MIN6 Cells.

Mitochondrial dynamics and bioenergetics are central to glucose-stimulated insulin secretion by pancreatic beta cells. Previously, we demonstrated that a disturbance in glucose-invoked fission impairs insulin secretion by compromising glucose catabolism. Here, we investigated whether the overexpression of mitochondrial fission regulator in MIN6 cells can improve or rescue insulin secretion. Although overexpression slightly improves the triggering mechanism of insulin secretion of the -knockdown cells and has no adverse effects on mitochondrial metabolism in wildtype MIN6 cells, the constitutive presence of unexpectedly impairs insulin content, which leads to a reduction in the absolute values of secreted insulin. Coherent with previous studies in -overexpressing muscle cells, we found that the upregulation of ER stress-related genes (, , and ) possibly impacts insulin production in MIN6 cells. Collectively, we confirm the important role of for the energy-coupling of insulin secretion but unravel off-targets effects by overexpression on insulin content that warrant caution when manipulating in disease therapy.