PuSH - Publication Server of Helmholtz Zentrum München: Positive feedback amplifies the response of mitochondrial membrane potential to glucose concentration in clonal pancreatic beta cells.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

EVA: Electronic Publishing

New EVA Application

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Gerencser, A.A.* ; Mookerjee, S.A.* ; Jastroch, M. ; Brand, M.D.*

Positive feedback amplifies the response of mitochondrial membrane potential to glucose concentration in clonal pancreatic beta cells.

Biochim. Biophys. Acta 1863, 1054-1065 (2016)

Publ. Version/Full Text

Research data

DOI

PMC

Open Access Green as soon as Postprint is submitted to ZB.

Abstract
Metrics
Extra information

Analysis of the cellular mechanisms of metabolic disorders, including type 2 diabetes mellitus, is complicated by the large number of reactions and interactions in metabolic networks. Metabolic control analysis with appropriate modularization is a powerful method for simplifying and analyzing these networks. To analyze control of cellular energy metabolism in adherent cell cultures of the INS-1 832/13 pancreatic β-cell model we adapted our microscopy assay of absolute mitochondrial membrane potential (δψM) to a fluorescence microplate reader format, and applied it in conjunction with cell respirometry. In these cells the sensitive response of δψM to extracellular glucose concentration drives glucose-stimulated insulin secretion. Using metabolic control analysis we identified the control properties that generate this sensitive response. Force-flux relationships between δψM and respiration were used to calculate kinetic responses to δψM of processes both upstream (glucose oxidation) and downstream (proton leak and ATP turnover) of δψM. The analysis revealed that glucose-evoked δψM hyperpolarization is amplified by increased glucose oxidation activity caused by factors downstream of δψM. At high glucose, the hyperpolarized δψM is stabilized almost completely by the action of glucose oxidation, whereas proton leak also contributes to the homeostatic control of δψM at low glucose. These findings suggest a strong positive feedback loop in the regulation of β-cell energetics, and a possible regulatory role of proton leak in the fasting state. Analysis of islet bioenergetics from published cases of type 2 diabetes suggests that disruption of this feedback can explain the damaged bioenergetic response of β-cells to glucose.

Impact Factor

Scopus SNIP

Web of Science
Times Cited

Scopus
Cited By

Altmetric

5.373

1.351