Regulation of glucose-stimulated insulin secretion by ATPase Inhibitory Factor 1 (IF1)

0490334 - FGÚ 2019 RIV GB eng J - Journal Article
Kahancová, Anežka - Sklenář, Filip - Ježek, Petr - Dlasková, Andrea
Regulation of glucose-stimulated insulin secretion by ATPase Inhibitory Factor 1 (IF1).
FEBS Letters. Roč. 592, č. 6 (2018), s. 999-1009. ISSN 0014-5793. E-ISSN 1873-3468
R&D Projects: GA MŠMT(CZ) LM2015062; GA ČR(CZ) GJ15-02022Y
Institutional support: RVO:67985823
Keywords : ATP synthase * diabetes * IF1 * INS-1E cells * insulin secretion * beta-cells
OECD category: Biochemistry and molecular biology
Impact factor: 2.675, year: 2018

ATPase Inhibitory factor 1 (IF1) is an endogenous regulator of mitochondrial ATP synthase, which is involved in cellular metabolism. Although great progress has been made, biological roles of IF1 and molecular mechanisms of its action are still to be elucidated. Here, we show that IF1 is present in pancreatic beta-cells, bound to the ATP synthase also under normal physiological conditions. IF1 silencing in model pancreatic beta-cells (INS-1E) increases insulin secretion over a range of glucose concentrations. The left-shifted dose-response curve reveals excessive insulin secretion even under low glucose, corresponding to fasting conditions. A parallel increase in cellular respiration and ATP levels is observed. To conclude, our results indicate that IF1 is a negative regulator of insulin secretion involved in pancreatic beta-cell glucose sensing.
Permanent Link: http://hdl.handle.net/11104/0284583