Difference between revisions of "Franko 2012 J Mol Med"
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{{Publication | {{Publication | ||
|title=Franko A, von Kleist-Retzow JC, Böse M, Sanchez-Lasheras C, Brodesser S, Krut O, Kunz WS, Wiedermann D, Hoehn M, Stöhr 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 (Berl) [Epub ahead of print].  | |title=Franko A, von Kleist-Retzow JC, Böse M, Sanchez-Lasheras C, Brodesser S, Krut O, Kunz WS, Wiedermann D, Hoehn M, Stöhr 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 (Berl) [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, Böse M, Sanchez-Lasheras C, Brodesser S, Krut O, Kunz WS, Wiedermann D, Hoehn M, Stöhr O, Moll L, Freude S, Krone W, Schubert M, Wiesner RJ | |authors=Franko A, von Kleist-Retzow JC, Böse M, Sanchez-Lasheras C, Brodesser S, Krut O, Kunz WS, Wiedermann D, Hoehn M, Stöhr O, Moll L, Freude S, Krone W, Schubert M, Wiesner RJ | ||
| Line 7: | Line 7: | ||
|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-1α 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-1α 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 | ||
|mipnetlab=DE Cologne Larsson NG | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
Revision as of 13:07, 2 April 2012
| Franko A, von Kleist-Retzow JC, Böse M, Sanchez-Lasheras C, Brodesser S, Krut O, Kunz WS, Wiedermann D, Hoehn M, Stöhr 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 (Berl) [Epub ahead of print]. |
Franko A, von Kleist-Retzow JC, Böse M, Sanchez-Lasheras C, Brodesser S, Krut O, Kunz WS, Wiedermann D, Hoehn M, Stöhr O, Moll L, Freude S, Krone W, Schubert M, Wiesner RJ (2012) J Mol Med (Berl)
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-1α 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
âą O2k-Network Lab: DE Cologne Larsson NG
Labels:
Stress:Mitochondrial Disease; Degenerative Disease and Defect"Mitochondrial Disease; Degenerative Disease and Defect" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property., Genetic Defect; Knockdown; Overexpression"Genetic Defect; Knockdown; Overexpression" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Mouse Tissue;cell: z in prep"z in prep" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property., Skeletal Muscle"Skeletal Muscle" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property.
Enzyme: z in prep"z in prep" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property. Regulation: z in prep"z in prep" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
HRR: Oxygraph-2k
