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

被引：36

作者：

Kahancova, Anezka ^{[1
]}

Sklenar, Filip ^{[1
]}

Jezek, Petr ^{[1
]}

Dlaskova, Andrea ^{[1
]}

机构：

[1] Czech Acad Sci, Inst Physiol, Dept Mitochondrial Physiol, 75,Videnska 1083, Prague 14220 4, Czech Republic

来源：

FEBS LETTERS | 2018年 / 592卷 / 06期

关键词：

ATP synthase; diabetes; IF1; INS-1E cells; insulin secretion; beta-cells; PANCREATIC BETA-CELLS; SUPERRESOLUTION MICROSCOPY REVEALS; ACTIVATED PROTEIN-KINASE; MITOCHONDRIAL ATPASE; ENERGY-METABOLISM; OXIDATIVE-PHOSPHORYLATION; DOWN-REGULATION; CARDIAC-MUSCLE; CANCER-CELLS; BOVINE IF1;

D O I：

10.1002/1873-3468.12991

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：999 / 1009

页数：11

共 49 条

[1] A functionally active human F1F0 ATPase can be purified by immunocapture from heart tissue and fibroblast cell lines [J].