Journal article
Insulin Stimulates Mitochondrial Fusion and Function in Cardiomyocytes via the Akt-mTOR-NFκB-Opa-1 Signaling Pathway
Diabetes (New York, N.Y.), Vol.63(1), pp.75-88
01/2014
DOI: 10.2337/db13-0340
PMCID: PMC3868041
PMID: 24009260
Abstract
Insulin regulates heart metabolism through the regulation of insulin-stimulated glucose uptake. Studies have indicated that insulin can also regulate mitochondrial function. Relevant to this idea, mitochondrial function is impaired in diabetic individuals. Furthermore, the expression of Opa-1 and mitofusins, proteins of the mitochondrial fusion machinery, is dramatically altered in obese and insulin-resistant patients. Given the role of insulin in the control of cardiac energetics, the goal of this study was to investigate whether insulin affects mitochondrial dynamics in cardiomyocytes. Confocal microscopy and the mitochondrial dye MitoTracker Green were used to obtain three-dimensional images of the mitochondrial network in cardiomyocytes and L6 skeletal muscle cells in culture. Three hours of insulin treatment increased Opa-1 protein levels, promoted mitochondrial fusion, increased mitochondrial membrane potential, and elevated both intracellular ATP levels and oxygen consumption in cardiomyocytes in vitro and in vivo
.
Consequently, the silencing of Opa-1 or Mfn2 prevented all the metabolic effects triggered by insulin. We also provide evidence indicating that insulin increases mitochondrial function in cardiomyocytes through the Akt-mTOR-NFκB signaling pathway. These data demonstrate for the first time in our knowledge that insulin acutely regulates mitochondrial metabolism in cardiomyocytes through a mechanism that depends on increased mitochondrial fusion, Opa-1, and the Akt-mTOR-NFκB pathway.
Details
- Title: Subtitle
- Insulin Stimulates Mitochondrial Fusion and Function in Cardiomyocytes via the Akt-mTOR-NFκB-Opa-1 Signaling Pathway
- Creators
- Valentina Parra - Advanced Center for Chronic Diseases (ACCDIS), Facultad de Ciencias Químicas y Farmacéuticas & Facultad de Medicina, Universidad de Chile, Santiago, ChileHugo E Verdejo - Advanced Center for Chronic Diseases (ACCDIS), Facultad de Ciencias Químicas y Farmacéuticas & Facultad de Medicina, Universidad de Chile, Santiago, ChileMyriam Iglewski - Department of Internal Medicine (Cardiology) and Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TXAndrea del Campo - Advanced Center for Chronic Diseases (ACCDIS), Facultad de Ciencias Químicas y Farmacéuticas & Facultad de Medicina, Universidad de Chile, Santiago, ChileRodrigo Troncoso - Advanced Center for Chronic Diseases (ACCDIS), Facultad de Ciencias Químicas y Farmacéuticas & Facultad de Medicina, Universidad de Chile, Santiago, ChileDeborah Jones - Program in Molecular Medicine and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UTYi Zhu - Program in Molecular Medicine and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UTJovan Kuzmicic - Advanced Center for Chronic Diseases (ACCDIS), Facultad de Ciencias Químicas y Farmacéuticas & Facultad de Medicina, Universidad de Chile, Santiago, ChileChristian Pennanen - Advanced Center for Chronic Diseases (ACCDIS), Facultad de Ciencias Químicas y Farmacéuticas & Facultad de Medicina, Universidad de Chile, Santiago, ChileCamila Lopez‑Crisosto - Advanced Center for Chronic Diseases (ACCDIS), Facultad de Ciencias Químicas y Farmacéuticas & Facultad de Medicina, Universidad de Chile, Santiago, ChileFabián Jaña - Programa de Farmacología Molecular y Clínica, Facultad de Medicina, Universidad de Chile, Santiago, ChileJorge Ferreira - Programa de Farmacología Molecular y Clínica, Facultad de Medicina, Universidad de Chile, Santiago, ChileEduard Noguera - Institute for Research in Biomedicine, Barcelona, SpainMario Chiong - Advanced Center for Chronic Diseases (ACCDIS), Facultad de Ciencias Químicas y Farmacéuticas & Facultad de Medicina, Universidad de Chile, Santiago, ChileDavid A Bernlohr - Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota: Twin Cities, Minneapolis, MNAmira Klip - The Hospital for Sick Children, Toronto, Ontario, CanadaJoseph A Hill - Department of Internal Medicine (Cardiology) and Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TXBeverly A Rothermel - Department of Internal Medicine (Cardiology) and Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TXEvan Dale Abel - Program in Molecular Medicine and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UTAntonio Zorzano - Institute for Research in Biomedicine, Barcelona, SpainSergio Lavandero - Advanced Center for Chronic Diseases (ACCDIS), Facultad de Ciencias Químicas y Farmacéuticas & Facultad de Medicina, Universidad de Chile, Santiago, Chile
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.63(1), pp.75-88
- DOI
- 10.2337/db13-0340
- PMID
- 24009260
- PMCID
- PMC3868041
- NLM abbreviation
- Diabetes
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Publisher
- American Diabetes Association
- Language
- English
- Date published
- 01/2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984025268702771
Metrics
28 Record Views