Overexpression of native IF1 downregulates glucose-stimulated insulin secretion by pancreatic INS-1E cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F20%3A00532331" target="_blank" >RIV/67985823:_____/20:00532331 - isvavai.cz</a>

Result on the web

<a href="https://www.nature.com/articles/s41598-020-58411-x" target="_blank" >https://www.nature.com/articles/s41598-020-58411-x</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-020-58411-x" target="_blank" >10.1038/s41598-020-58411-x</a>

Result language

angličtina

Original language name

Overexpression of native IF1 downregulates glucose-stimulated insulin secretion by pancreatic INS-1E cells

Original language description

We have previously reported that transient knock-down of ATPase inhibitory factor 1 (IF1) by siRNA upregulates ATP levels and subsequently augments insulin secretion in model pancreatic beta-cells INS-1E. Here we investigated how long-term IF1-overexpression impacts pancreatic beta-cell bioenergetics and insulin secretion. We generated INS-1E cell line stably overexpressing native IF1. We revealed that IF1 overexpression leads to a substantial decrease in ATP levels and reduced glucose-stimulated insulin secretion. A decrease in total cellular ATP content was also reflected in decreased free ATP cytosolic and mitochondrial levels, as monitored with ATeam biosensor. Consistently, cellular respiration of IF1-overexpressing cells was decreased. 3D structured illumination microscopy (SIM) revealed a higher amount of insulin granules with higher volume in IF1-overexpressing cells. Similar effects occurred when cells were incubated at low glucose concentrations. Noteworthy, activation of PKA by dibutyryl cAMP entirely abolished the inhibitory effect of IF1 overexpression on ATP production and insulin secretion. Mitochondrial network morphology and cristae ultrastructure in INS-1E overexpressing IF1 remained mostly unchanged. Finally, we show that INS-1E cells decrease their IF1 protein levels relative to ATP synthase alpha-subunit in response to increased glucose. In conclusion, IF1 actively downregulates INS-1E cellular metabolism and reduces their ability to secrete insulin.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Scientific Reports

ISSN

2045-2322

e-ISSN

—

Volume of the periodical

10

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

1551

UT code for WoS article

000562876200007

EID of the result in the Scopus database

2-s2.0-85078837861