RRC ID 37642
Author Mitsuishi M, Miyashita K, Muraki A, Itoh H.
Title Angiotensin II reduces mitochondrial content in skeletal muscle and affects glycemic control.
Journal Diabetes
Abstract OBJECTIVE:Blockade of angiotensin (Ang) II has been shown to prevent new-onset type 2 diabetes. We focused on the effects of AngII on muscle mitochondria, especially on their biogenesis, as an underlining mechanism of type 2 diabetes.
RESEARCH DESIGN AND METHODS:C2C12 cells and C57bl/6 mice were used to examine roles for AngII in the regulation of muscle mitochondria and to explore whether the effect was mediated by type 1 AngII receptor (AT1R) or type 2 receptor (AT2R).
RESULTS:C2C12 cells treated with 10(-8)-10(-6) mol/l AngII reduced the mitochondrial content associated with downregulation of the genes involved in mitochondrial biogenesis. The action of AngII was diminished by blockade of AT2R but not AT1R, whereas overexpression of AT2R augmented the effect. AngII increased mitochondrial ROS and decreased mitochondrial membrane potential, and these effects of AngII were significantly suppressed by blockade of either AT1R or AT2R. Chronic AngII infusion in mice also reduced muscle mitochondrial content in association with increased intramuscular triglyceride and deteriorated glycemic control. The AngII-induced reduction in muscle mitochondria in mice was partially, but significantly, reversed by blockade of either AT1R or AT2R, associated with increased fat oxidation, decreased muscle triglyceride, and improved glucose tolerance. Genes involved in mitochondrial biogenesis were decreased via AT2R but not AT1R under these in vivo conditions.
CONCLUSIONS:Taken together, these findings imply the novel roles for AngII in the regulation of muscle mitochondria and lipid metabolism. AngII reduces mitochondrial content possibly through AT1R-dependent augmentation of their degradation and AT2R-dependent direct suppression of their biogenesis.
Volume 58(3)
Pages 710-7
Published 2009-3
DOI 10.2337/db08-0949
PII db08-0949
PMID 19074984
PMC PMC2646070
MeSH Angiotensin II / pharmacology* Animals Calorimetry, Indirect Cell Line DNA, Mitochondrial / genetics Gene Expression / drug effects Glucose Tolerance Test Membrane Potentials Mice Mice, Inbred C57BL Mitochondria, Muscle / drug effects Mitochondria, Muscle / metabolism* Oligonucleotide Array Sequence Analysis Polymerase Chain Reaction RNA Interference Receptor, Angiotensin, Type 1 / drug effects Receptor, Angiotensin, Type 1 / genetics Receptor, Angiotensin, Type 1 / physiology* Receptor, Angiotensin, Type 2 / drug effects Receptor, Angiotensin, Type 2 / genetics Receptor, Angiotensin, Type 2 / physiology*
IF 7.273
Times Cited 33
Human and Animal Cells