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.
journal_name
Diabetesjournal_title
Diabetesauthors
Parra V,Verdejo HE,Iglewski M,Del Campo A,Troncoso R,Jones D,Zhu Y,Kuzmicic J,Pennanen C,Lopez-Crisosto C,Jaña F,Ferreira J,Noguera E,Chiong M,Bernlohr DA,Klip A,Hill JA,Rothermel BA,Abel ED,Zorzano A,Lavandero Sdoi
10.2337/db13-0340subject
Has Abstractpub_date
2014-01-01 00:00:00pages
75-88issue
1eissn
0012-1797issn
1939-327Xpii
db13-0340journal_volume
63pub_type
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