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PRAS40 prevents development of diabetic cardiomyopathy and improves hepatic insulin sensitivity in obesity

Abstract Diabetes is a multi-organ disease and diabetic cardiomyopathy can result in heart failure, which is a leading cause of morbidity and mortality in diabetic patients. In the liver, insulin resistance contributes to hyperglycaemia and hyperlipidaemia, which further worsens the metabolic profil...

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Hauptverfasser: Völkers, Mirko (VerfasserIn) , Doroudgar, Shirin (VerfasserIn) , Nguyen, Nathalie (VerfasserIn) , Konstandin, Mathias H (VerfasserIn) , Quijada, Pearl (VerfasserIn) , Din, Shabana (VerfasserIn) , Ornelas, Luis (VerfasserIn) , Thuerauf, Donna J (VerfasserIn) , Gude, Natalie (VerfasserIn) , Friedrich, Kilian (VerfasserIn) , Herzig, Stephan (VerfasserIn) , Glembotski, Christopher C (VerfasserIn) , Sussman, Mark A (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2014
In: EMBO molecular medicine
Year: 2013, Jahrgang: 6, Heft: 1, Pages: 57-65
ISSN:1757-4684
DOI:10.1002/emmm.201303183
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/emmm.201303183
Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.1002/emmm.201303183
Volltext
Verfasserangaben:Mirko Völkers, Shirin Doroudgar, Nathalie Nguyen, Mathias H Konstandin, Pearl Quijada, Shabana Din, Luis Ornelas, Donna J Thuerauf, Natalie Gude, Kilian Friedrich, Stephan Herzig, Christopher C Glembotski & Mark A Sussman
Beschreibung
Zusammenfassung:Abstract Diabetes is a multi-organ disease and diabetic cardiomyopathy can result in heart failure, which is a leading cause of morbidity and mortality in diabetic patients. In the liver, insulin resistance contributes to hyperglycaemia and hyperlipidaemia, which further worsens the metabolic profile. Defects in mTOR signalling are believed to contribute to metabolic dysfunctions in diabetic liver and hearts, but evidence is missing that mTOR activation is causal to the development of diabetic cardiomyopathy. This study shows that specific mTORC1 inhibition by PRAS40 prevents the development of diabetic cardiomyopathy. This phenotype was associated with improved metabolic function, blunted hypertrophic growth and preserved cardiac function. In addition PRAS40 treatment improves hepatic insulin sensitivity and reduces systemic hyperglycaemia in obese mice. Thus, unlike rapamycin, mTORC1 inhibition with PRAS40 improves metabolic profile in diabetic mice. These findings may open novel avenues for therapeutic strategies using PRAS40 directed against diabetic-related diseases.
Beschreibung:Published online 31 October 2013
Gesehen am 27.10.2020
Beschreibung:Online Resource
ISSN:1757-4684
DOI:10.1002/emmm.201303183

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