Franko 2012 J Mol Med: Difference between revisions
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|title=Franko A, von Kleist-Retzow JC, BΓΆse M, Sanchez-Lasheras C, Brodesser S, Krut O, Kunz WS, Wiedermann D, Hoehn M, StΓΆhr O, Moll L, Freude S, Krone W, Schubert M, Wiesner RJ (2012) Complete failure of insulin-transmitted signaling, but not obesity-induced insulin resistance, impairs respiratory chain function in muscle. J Mol Med | |title=Franko A, von Kleist-Retzow JC, BΓΆse M, Sanchez-Lasheras C, Brodesser S, Krut O, Kunz WS, Wiedermann D, Hoehn M, StΓΆhr O, Moll L, Freude S, Krone W, Schubert M, Wiesner RJ (2012) Complete failure of insulin-transmitted signaling, but not obesity-induced insulin resistance, impairs respiratory chain function in muscle. J Mol Med [Epub ahead of print]. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed?term=Complete%20failure%20of%20insulin-transmitted%20signaling%2C%20but%20not%20obesity-induced%20insulin%20resistance%2C%20impairs%20respiratory%20chain%20function%20in%20muscle%20 PMID: 22411022] | |info=[http://www.ncbi.nlm.nih.gov/pubmed?term=Complete%20failure%20of%20insulin-transmitted%20signaling%2C%20but%20not%20obesity-induced%20insulin%20resistance%2C%20impairs%20respiratory%20chain%20function%20in%20muscle%20 PMID: 22411022] | ||
|authors=Franko A, von Kleist-Retzow JC, BΓΆse M, Sanchez-Lasheras C, Brodesser S, Krut O, Kunz WS, Wiedermann D, Hoehn M, StΓΆhr O, Moll L, Freude S, Krone W, Schubert M, Wiesner RJ | |authors=Franko A, von Kleist-Retzow JC, BΓΆse M, Sanchez-Lasheras C, Brodesser S, Krut O, Kunz WS, Wiedermann D, Hoehn M, StΓΆhr O, Moll L, Freude S, Krone W, Schubert M, Wiesner RJ | ||
|year=2012 | |year=2012 | ||
|journal=J Mol Med | |journal=J Mol Med | ||
|abstract=The role of mitochondrial dysfunction in the development of insulin resistance and type 2 diabetes remains controversial. In order to specifically define the relationship between insulin receptor (InsR) signaling, insulin resistance, hyperglycemia, hyperlipidemia and mitochondrial function, we analyzed mitochondrial performance of insulin-sensitive, slow-oxidative muscle in four different mouse models. In obese but normoglycemic ob/ob mice as well as in obese but diabetic mice under high-fat diet, mitochondrial performance remained unchanged even though intramyocellular diacylglycerols (DAGs), triacylglycerols (TAGs), and ceramides accumulated. In contrast, in muscle-specific InsR knockout (MIRKO) and streptozotocin (STZ)-treated hypoinsulinemic, hyperglycemic mice, levels of mitochondrial respiratory chain complexes and mitochondrial function were markedly reduced. In STZ, but not in MIRKO mice, this was caused by reduced transcription of mitochondrial genes mediated via decreased PGC-1Ξ± expression. We conclude that mitochondrial dysfunction is not causally involved in the pathogenesis of obesity-associated insulin resistance under normoglycemic conditions. However, obesity-associated type 2 diabetes and accumulation of DAGs or TAGs is not associated with impaired mitochondrial function. In contrast, chronic hypoinsulinemia and hyperglycemia as seen in STZ-treated mice as well as InsR deficiency in muscle of MIRKO mice lead to mitochondrial dysfunction. We postulate that decreased mitochondrial mass and/or performance in skeletal muscle of non-diabetic, obese or type 2 diabetic, obese patients observed in clinical studies must be explained by genetic predisposition, physical inactivity, or other still unknown factors. | |abstract=The role of mitochondrial dysfunction in the development of insulin resistance and type 2 diabetes remains controversial. In order to specifically define the relationship between insulin receptor (InsR) signaling, insulin resistance, hyperglycemia, hyperlipidemia and mitochondrial function, we analyzed mitochondrial performance of insulin-sensitive, slow-oxidative muscle in four different mouse models. In obese but normoglycemic ob/ob mice as well as in obese but diabetic mice under high-fat diet, mitochondrial performance remained unchanged even though intramyocellular diacylglycerols (DAGs), triacylglycerols (TAGs), and ceramides accumulated. In contrast, in muscle-specific InsR knockout (MIRKO) and streptozotocin (STZ)-treated hypoinsulinemic, hyperglycemic mice, levels of mitochondrial respiratory chain complexes and mitochondrial function were markedly reduced. In STZ, but not in MIRKO mice, this was caused by reduced transcription of mitochondrial genes mediated via decreased PGC-1Ξ± expression. We conclude that mitochondrial dysfunction is not causally involved in the pathogenesis of obesity-associated insulin resistance under normoglycemic conditions. However, obesity-associated type 2 diabetes and accumulation of DAGs or TAGs is not associated with impaired mitochondrial function. In contrast, chronic hypoinsulinemia and hyperglycemia as seen in STZ-treated mice as well as InsR deficiency in muscle of MIRKO mice lead to mitochondrial dysfunction. We postulate that decreased mitochondrial mass and/or performance in skeletal muscle of non-diabetic, obese or type 2 diabetic, obese patients observed in clinical studies must be explained by genetic predisposition, physical inactivity, or other still unknown factors. | ||
|keywords=Type 2 diabetes mellitus, mitochondrial biogenesis, mitochondrial gene expression, insulin receptor, muscle metabolism, in vivo NMR spectroscopy, lipid metabolism, ceramides, ob/ob mice, muscle-specific InsR knockout (MIRKO) mice | |keywords=Type 2 diabetes mellitus, mitochondrial biogenesis, mitochondrial gene expression, insulin receptor, muscle metabolism, in vivo NMR spectroscopy, lipid metabolism, ceramides, ob/ob mice, muscle-specific InsR knockout (MIRKO) mice | ||
Revision as of 13:09, 2 April 2012
| [[Has title::Franko A, von Kleist-Retzow JC, BΓΆse M, Sanchez-Lasheras C, Brodesser S, Krut O, Kunz WS, Wiedermann D, Hoehn M, StΓΆhr O, Moll L, Freude S, Krone W, Schubert M, Wiesner RJ (2012) Complete failure of insulin-transmitted signaling, but not obesity-induced insulin resistance, impairs respiratory chain function in muscle. J Mol Med [Epub ahead of print].]] |
Β» [[Has info::PMID: 22411022]]
Franko A, von Kleist-Retzow JC, BΓΆse M, Sanchez-Lasheras C, Brodesser S, Krut O, Kunz WS, Wiedermann D, Hoehn M, StΓΆhr O, Moll L, Freude S, Krone W, Schubert M, Wiesner RJ (2012) J Mol Med
Abstract: The role of mitochondrial dysfunction in the development of insulin resistance and type 2 diabetes remains controversial. In order to specifically define the relationship between insulin receptor (InsR) signaling, insulin resistance, hyperglycemia, hyperlipidemia and mitochondrial function, we analyzed mitochondrial performance of insulin-sensitive, slow-oxidative muscle in four different mouse models. In obese but normoglycemic ob/ob mice as well as in obese but diabetic mice under high-fat diet, mitochondrial performance remained unchanged even though intramyocellular diacylglycerols (DAGs), triacylglycerols (TAGs), and ceramides accumulated. In contrast, in muscle-specific InsR knockout (MIRKO) and streptozotocin (STZ)-treated hypoinsulinemic, hyperglycemic mice, levels of mitochondrial respiratory chain complexes and mitochondrial function were markedly reduced. In STZ, but not in MIRKO mice, this was caused by reduced transcription of mitochondrial genes mediated via decreased PGC-1Ξ± expression. We conclude that mitochondrial dysfunction is not causally involved in the pathogenesis of obesity-associated insulin resistance under normoglycemic conditions. However, obesity-associated type 2 diabetes and accumulation of DAGs or TAGs is not associated with impaired mitochondrial function. In contrast, chronic hypoinsulinemia and hyperglycemia as seen in STZ-treated mice as well as InsR deficiency in muscle of MIRKO mice lead to mitochondrial dysfunction. We postulate that decreased mitochondrial mass and/or performance in skeletal muscle of non-diabetic, obese or type 2 diabetic, obese patients observed in clinical studies must be explained by genetic predisposition, physical inactivity, or other still unknown factors. β’ Keywords: Type 2 diabetes mellitus, mitochondrial biogenesis, mitochondrial gene expression, insulin receptor, muscle metabolism, in vivo NMR spectroscopy, lipid metabolism, ceramides, ob/ob mice, muscle-specific InsR knockout (MIRKO) mice
β’ O2k-Network Lab: DE Cologne Larsson NG
Labels:
Stress:Mitochondrial Disease; Degenerative Disease and Defect, Genetic Defect; Knockdown; Overexpression Organism: Mouse Tissue;cell: z in prep, Skeletal Muscle
Enzyme: z in prep Regulation: z in prep
HRR: Oxygraph-2k
