Difference between revisions of "Spacek 2008 Int J Biochem Cell Biol"
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{{Publication | {{Publication | ||
|title=Spacek T, | |title=Spacek T, Santorová J, Zacharovová K, Berková Z, Hlavatá L, Saudek F, Jezek P (2008) Glucose-stimulated insulin secretion of insulinoma INS-1E cells is associated with elevation of both respiration and mitochondrial membrane potential. Int J Biochem Cell Biol 40:1522-35. | ||
|authors=Spacek T, Santorova J, Zacharovova K, Berkova Z, Hlavata L, Saudek F, Jezek P | |info=[http://www.ncbi.nlm.nih.gov/pubmed/18248766 PMID: 18248766] | ||
|authors=Spacek T, Santorova J, Zacharovova K, Berkova Z, Hlavata L, Saudek F, Jezek P | |||
|year=2008 | |year=2008 | ||
|journal= | |journal=Int J Biochem Cell Biol | ||
| | |abstract=Increased ATP/ADP ratio resulting from enhanced glycolysis and oxidative phosphorylation represents a plausible mechanism controlling the glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells. Although specific bioenergetics might be involved, parallel studies of cell respiration and mitochondrial membrane potential (DeltaPsi(m)) during GSIS are lacking. Using high resolution respirometry and parallel DeltaPsi(m) monitoring by two distinct fluorescence probes we have quantified bioenergetics in rat insulinoma INS-1E cells representing a suitable model to study ''in vitro'' insulin secretion. Upon glucose addition to glucose-depleted cells we demonstrated a simultaneous increase in respiration and DeltaPsi(m) during GSIS and showed that the endogenous state 3/state 4 respiratory ratio hyperbolically increased with glucose, approaching the maximum oxidative phosphorylation rate at maximum GSIS. Attempting to assess the basis of the "toxic" effect of fatty acids on insulin secretion, GSIS was studied after linoleic acid addition, which diminished respiration increase, DeltaPsi(m) jump, and magnitude of insulin release, and reduced state 3/state 4 dependencies on glucose. Its effects were due to protonophoric function, i.e. uncoupling, since without glucose, linoleic acid accelerated both state 3 and state 4 respiration by similar extent. In turn, state 3 respiration increased marginally with linoleic acid at 10-20mM glucose. We conclude that upon glucose addition in physiological range, the INS-1E cells are able to regulate the oxidative phosphorylation rate from nearly zero to maximum and that the impairment of GSIS by linoleic acid is caused by mitochondrial uncoupling. These findings may be relevant to the pathogenesis of type 2 diabetes. | ||
|keywords=Beta cells, INS-1E cells, In situ mitochondrial respiration, In situ mitochondrial membrane potential, Glucose-stimulated insulin secretion | |||
|mipnetlab=CZ Prague Jezek P | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |||
|diseases=Diabetes | |||
|organism=Rat | |||
|tissues=Islet cell;pancreas;thymus, Other cell lines | |||
|preparations=Intact cells | |||
|couplingstates=LEAK, ROUTINE, ET | |||
|pathways=ROX | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} | ||
Latest revision as of 16:10, 13 November 2017
| Spacek T, Santorová J, Zacharovová K, Berková Z, Hlavatá L, Saudek F, Jezek P (2008) Glucose-stimulated insulin secretion of insulinoma INS-1E cells is associated with elevation of both respiration and mitochondrial membrane potential. Int J Biochem Cell Biol 40:1522-35. |
Spacek T, Santorova J, Zacharovova K, Berkova Z, Hlavata L, Saudek F, Jezek P (2008) Int J Biochem Cell Biol
Abstract: Increased ATP/ADP ratio resulting from enhanced glycolysis and oxidative phosphorylation represents a plausible mechanism controlling the glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells. Although specific bioenergetics might be involved, parallel studies of cell respiration and mitochondrial membrane potential (DeltaPsi(m)) during GSIS are lacking. Using high resolution respirometry and parallel DeltaPsi(m) monitoring by two distinct fluorescence probes we have quantified bioenergetics in rat insulinoma INS-1E cells representing a suitable model to study in vitro insulin secretion. Upon glucose addition to glucose-depleted cells we demonstrated a simultaneous increase in respiration and DeltaPsi(m) during GSIS and showed that the endogenous state 3/state 4 respiratory ratio hyperbolically increased with glucose, approaching the maximum oxidative phosphorylation rate at maximum GSIS. Attempting to assess the basis of the "toxic" effect of fatty acids on insulin secretion, GSIS was studied after linoleic acid addition, which diminished respiration increase, DeltaPsi(m) jump, and magnitude of insulin release, and reduced state 3/state 4 dependencies on glucose. Its effects were due to protonophoric function, i.e. uncoupling, since without glucose, linoleic acid accelerated both state 3 and state 4 respiration by similar extent. In turn, state 3 respiration increased marginally with linoleic acid at 10-20mM glucose. We conclude that upon glucose addition in physiological range, the INS-1E cells are able to regulate the oxidative phosphorylation rate from nearly zero to maximum and that the impairment of GSIS by linoleic acid is caused by mitochondrial uncoupling. These findings may be relevant to the pathogenesis of type 2 diabetes. • Keywords: Beta cells, INS-1E cells, In situ mitochondrial respiration, In situ mitochondrial membrane potential, Glucose-stimulated insulin secretion
• O2k-Network Lab: CZ Prague Jezek P
Labels: MiParea: Respiration
Pathology: Diabetes
Organism: Rat Tissue;cell: Islet cell;pancreas;thymus, Other cell lines Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ET
Pathway: ROX
HRR: Oxygraph-2k
