Glucose stimulation induces dynamic change of mitochondrial morphology to promote insulin secretion in the insulinoma cell line INS-1E.

Authors

Bong Sook Jhun, Center for Translational Medicine, Department of Medicine, Thomas Jefferson UniversityFollow
Hakjoo Lee, Department of Physiology, Medical College of Georgia, Georgia Regents UniversityFollow
Zheng-Gen Jin, Department of Medicine, University of Rochester School of Medicine and Dentistry; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and DentistryFollow
Yisang Yoon, Department of Physiology, Medical College of Georgia, Georgia Regents UniversityFollow

Document Type

Article

Publication Date

4-2-2013

Comments

This article has been peer reviewed and is published in PloS One.

Volume 8, Issue 4, 2 April 2013, Article numbere60810.

The published version is available at DOI: 10.1371/journal.pone.0060810. © 2013 Jhun et al.

Abstract

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.

Recommended Citation

Jhun, Bong Sook; Lee, Hakjoo; Jin, Zheng-Gen; and Yoon, Yisang, "Glucose stimulation induces dynamic change of mitochondrial morphology to promote insulin secretion in the insulinoma cell line INS-1E." (2013). Center for Translational Medicine Faculty Papers. Paper 25.
https://jdc.jefferson.edu/transmedfp/25

PubMed ID

23565276