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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:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
287
issue
19
pages
15706 - 15717
publisher
ASBMB
external identifiers
  • wos:000304006300049
  • pmid:22418435
  • scopus:84860847465
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
2012-04-03 11:01:44
date last changed
2017-08-06 04:44:40
@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    = {ASBMB},
  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},
  volume       = {287},
  year         = {2012},
}