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Glucose Stimulation Induces Dynamic Change of Mitochondrial Morphology to Promote Insulin Secretion in the Insulinoma Cell Line INS-1E

Fission and fusion of mitochondrial tubules are the major processes regulating mitochondrial morphology. However, the physiological significance of mitochondrial shape change is poorly understood. Glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells requires mitochondrial ATP production...

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Detalles Bibliográficos
Autores principales: Jhun, Bong Sook, Lee, Hakjoo, Jin, Zheng-Gen, Yoon, Yisang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614983/
https://www.ncbi.nlm.nih.gov/pubmed/23565276
http://dx.doi.org/10.1371/journal.pone.0060810
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author Jhun, Bong Sook
Lee, Hakjoo
Jin, Zheng-Gen
Yoon, Yisang
author_facet Jhun, Bong Sook
Lee, Hakjoo
Jin, Zheng-Gen
Yoon, Yisang
author_sort Jhun, Bong Sook
collection PubMed
description Fission and fusion of mitochondrial tubules are the major processes regulating mitochondrial morphology. However, the physiological significance of mitochondrial shape change is poorly understood. Glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells requires mitochondrial ATP production which evokes Ca(2+) influx through plasma membrane depolarization, triggering insulin vesicle exocytosis. Therefore, GSIS reflects mitochondrial function and can be used for evaluating functional changes associated with morphological alterations of mitochondria. Using the insulin-secreting cell line INS-1E, we found that glucose stimulation induced rapid mitochondrial shortening and recovery. Inhibition of mitochondrial fission through expression of the dominant-negative mutant DLP1-K38A eliminated this dynamic mitochondrial shape change and, importantly, blocked GSIS. We found that abolishing mitochondrial morphology change in glucose stimulation increased the mitochondrial inner membrane proton leak, and thus significantly diminished the mitochondrial ATP producing capacity in response to glucose stimulation. These results demonstrate that dynamic change of mitochondrial morphology is a previously unrecognized component for metabolism-secretion coupling of pancreatic β-cells by participating in efficient ATP production in response to elevated glucose levels.
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spelling pubmed-36149832013-04-05 Glucose Stimulation Induces Dynamic Change of Mitochondrial Morphology to Promote Insulin Secretion in the Insulinoma Cell Line INS-1E Jhun, Bong Sook Lee, Hakjoo Jin, Zheng-Gen Yoon, Yisang PLoS One Research Article Fission and fusion of mitochondrial tubules are the major processes regulating mitochondrial morphology. However, the physiological significance of mitochondrial shape change is poorly understood. Glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells requires mitochondrial ATP production which evokes Ca(2+) influx through plasma membrane depolarization, triggering insulin vesicle exocytosis. Therefore, GSIS reflects mitochondrial function and can be used for evaluating functional changes associated with morphological alterations of mitochondria. Using the insulin-secreting cell line INS-1E, we found that glucose stimulation induced rapid mitochondrial shortening and recovery. Inhibition of mitochondrial fission through expression of the dominant-negative mutant DLP1-K38A eliminated this dynamic mitochondrial shape change and, importantly, blocked GSIS. We found that abolishing mitochondrial morphology change in glucose stimulation increased the mitochondrial inner membrane proton leak, and thus significantly diminished the mitochondrial ATP producing capacity in response to glucose stimulation. These results demonstrate that dynamic change of mitochondrial morphology is a previously unrecognized component for metabolism-secretion coupling of pancreatic β-cells by participating in efficient ATP production in response to elevated glucose levels. Public Library of Science 2013-04-02 /pmc/articles/PMC3614983/ /pubmed/23565276 http://dx.doi.org/10.1371/journal.pone.0060810 Text en © 2013 Jhun et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Jhun, Bong Sook
Lee, Hakjoo
Jin, Zheng-Gen
Yoon, Yisang
Glucose Stimulation Induces Dynamic Change of Mitochondrial Morphology to Promote Insulin Secretion in the Insulinoma Cell Line INS-1E
title Glucose Stimulation Induces Dynamic Change of Mitochondrial Morphology to Promote Insulin Secretion in the Insulinoma Cell Line INS-1E
title_full Glucose Stimulation Induces Dynamic Change of Mitochondrial Morphology to Promote Insulin Secretion in the Insulinoma Cell Line INS-1E
title_fullStr Glucose Stimulation Induces Dynamic Change of Mitochondrial Morphology to Promote Insulin Secretion in the Insulinoma Cell Line INS-1E
title_full_unstemmed Glucose Stimulation Induces Dynamic Change of Mitochondrial Morphology to Promote Insulin Secretion in the Insulinoma Cell Line INS-1E
title_short Glucose Stimulation Induces Dynamic Change of Mitochondrial Morphology to Promote Insulin Secretion in the Insulinoma Cell Line INS-1E
title_sort glucose stimulation induces dynamic change of mitochondrial morphology to promote insulin secretion in the insulinoma cell line ins-1e
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614983/
https://www.ncbi.nlm.nih.gov/pubmed/23565276
http://dx.doi.org/10.1371/journal.pone.0060810
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