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 Drp1 in MIN6 cells can improve or rescue insulin secretion. Although Drp1 overexpression slightly improves the triggering mechanism of insulin secretion of the Drp1-knockdown cells and has no adverse effects on mitochondrial metabolism in wildtype MIN6 cells, the constitutive presence of Drp1 unexpectedly impairs insulin content, which leads to a reduction in the absolute values of secreted insulin. Coherent with previous studies in Drp1-overexpressing muscle cells, we found that the upregulation of ER stress-related genes (BiP, Chop, and Hsp60) possibly impacts insulin production in MIN6 cells. Collectively, we confirm the important role of Drp1 for the energy-coupling of insulin secretion but unravel off-targets effects by Drp1 overexpression on insulin content that warrant caution when manipulating Drp1 in disease therapy.
Bibliographical noteFunding Information:
This research was partially supported by the German Center for Diabetes Research (DZD) and Novo Nordisk Fonden (to M.J., grant number 0059646). P.-O.B. is supported by the Swedish Research Council.
© 2022 by the authors.
- Insulin Secretion
- Insulin-Secreting Cells/metabolism
- Mitochondrial Dynamics/genetics
- Insulin, Regular, Human
- glucose-stimulated insulin secretion
- insulin content
- MIN6 cell
- dynamin-related protein 1