Plasma Membrane Potential Oscillations in Insulin Secreting Ins-1 832/13 Cells do not Require Glycolysis and are not Initiated by Fluctuations in Mitochondrial Bioenergetics.
Goehring, Isabel ; Gerencser, Akos A ; Schmidt, Sara LU ; Brand, Martin D ; Mulder, Hindrik LU
and Nicholls, David
LU
(2012)
In Journal of Biological Chemistry
287(19).
p.15706-15717
- Abstract
- Oscillations in plasma membrane potential play a central role in glucose-induced insulin secretion from pancreatic β-cells and related insulinoma cell lines. We have employed a novel fluorescent plasma membrane potential (ψp) indicator in combination with indicators of cytoplasmic free Ca2+ ([Ca2+]c), mitochondrial membrane potential (ψm), matrix ATP concentration and NAD(P)H fluorescence to investigate the role of mitochondria in the generation of plasma membrane potential oscillations in clonal INS-1 832/13 β-cells. Elevated glucose caused oscillations in plasma membrane potential and cytoplasmic free Ca2+ concentration over the same concentration range required for insulin release, although considerable cell-to-cell heterogeneity was... (More)
- Oscillations in plasma membrane potential play a central role in glucose-induced insulin secretion from pancreatic β-cells and related insulinoma cell lines. We have employed a novel fluorescent plasma membrane potential (ψp) indicator in combination with indicators of cytoplasmic free Ca2+ ([Ca2+]c), mitochondrial membrane potential (ψm), matrix ATP concentration and NAD(P)H fluorescence to investigate the role of mitochondria in the generation of plasma membrane potential oscillations in clonal INS-1 832/13 β-cells. Elevated glucose caused oscillations in plasma membrane potential and cytoplasmic free Ca2+ concentration over the same concentration range required for insulin release, although considerable cell-to-cell heterogeneity was observed. Exogenous pyruvate was as effective as glucose in inducing oscillations, both in the presence and absence of 2.8mM glucose. Increased glucose and pyruvate each produced a concentration-dependent mitochondrial hyperpolarization. The causal relationships between pairs of parameters - ψp and [Ca2+]c, ψp and NAD(P)H, matrix ATP and [Ca2+]c, and ψm and [Ca2+]c were investigated at single cell level. It is concluded that, in these β-cells, depolarizing oscillations in ψp are not initiated by mitochondrial bioenergetic changes. Instead, regardless of substrate, it appears that the mitochondria may simply be required to exceed a critical bioenergetic threshold to allow release of insulin. Once this threshold is exceeded an autonomous ψp oscillatory mechanism is initiated. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2431815
- author
- Goehring, Isabel
; Gerencser, Akos A
; Schmidt, Sara
LU
; Brand, Martin D
; Mulder, Hindrik
LU
and Nicholls, David
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 287
- issue
- 19
- pages
- 15706 - 15717
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000304006300049
- pmid:22418435
- scopus:84860847465
- pmid:22418435
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M111.314567
- language
- English
- LU publication?
- yes
- id
- 968c342b-d1d8-4b35-864d-015910446fb1 (old id 2431815)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22418435?dopt=Abstract
- date added to LUP
- 2016-04-04 07:33:25
- date last changed
- 2024-02-10 20:13:52
@article{968c342b-d1d8-4b35-864d-015910446fb1,
abstract = {{Oscillations in plasma membrane potential play a central role in glucose-induced insulin secretion from pancreatic β-cells and related insulinoma cell lines. We have employed a novel fluorescent plasma membrane potential (ψp) indicator in combination with indicators of cytoplasmic free Ca2+ ([Ca2+]c), mitochondrial membrane potential (ψm), matrix ATP concentration and NAD(P)H fluorescence to investigate the role of mitochondria in the generation of plasma membrane potential oscillations in clonal INS-1 832/13 β-cells. Elevated glucose caused oscillations in plasma membrane potential and cytoplasmic free Ca2+ concentration over the same concentration range required for insulin release, although considerable cell-to-cell heterogeneity was observed. Exogenous pyruvate was as effective as glucose in inducing oscillations, both in the presence and absence of 2.8mM glucose. Increased glucose and pyruvate each produced a concentration-dependent mitochondrial hyperpolarization. The causal relationships between pairs of parameters - ψp and [Ca2+]c, ψp and NAD(P)H, matrix ATP and [Ca2+]c, and ψm and [Ca2+]c were investigated at single cell level. It is concluded that, in these β-cells, depolarizing oscillations in ψp are not initiated by mitochondrial bioenergetic changes. Instead, regardless of substrate, it appears that the mitochondria may simply be required to exceed a critical bioenergetic threshold to allow release of insulin. Once this threshold is exceeded an autonomous ψp oscillatory mechanism is initiated.}},
author = {{Goehring, Isabel and Gerencser, Akos A and Schmidt, Sara and Brand, Martin D and Mulder, Hindrik and Nicholls, David}},
issn = {{1083-351X}},
language = {{eng}},
number = {{19}},
pages = {{15706--15717}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Plasma Membrane Potential Oscillations in Insulin Secreting Ins-1 832/13 Cells do not Require Glycolysis and are not Initiated by Fluctuations in Mitochondrial Bioenergetics.}},
url = {{http://dx.doi.org/10.1074/jbc.M111.314567}},
doi = {{10.1074/jbc.M111.314567}},
volume = {{287}},
year = {{2012}},
}