e5a1ea5c51a86df57f697559cc3fedf5 224081.pdf 272bda3a7af5f5614cb3aab79ff9fd2e385fec7f 224081.pdf 05152a14c6fc3fd8005582b96a09854dad6e3780adf853e59ff2b26ab1722e94 224081.pdf Title: Contribution of Impaired Insulin Signaling to the Pathogenesis of Diabetic Cardiomyopathy Subject: Diabetic cardiomyopathy (DCM) has emerged as a relevant cause of heart failure among the diabetic population. Defined as a cardiac dysfunction that develops in diabetic patients independently of other major cardiovascular risks factors, such as high blood pressure and coronary artery disease, the underlying cause of DCMremains to be unveiled. Several pathogenic factors, including glucose and lipid toxicity, mitochondrial dysfunction, increased oxidative stress, sustained activation of the renin-angiotensin system (RAS) or altered calcium homeostasis, have been shown to contribute to the structural and functional alterations that characterize diabetic hearts. However, all these pathogenic mechanisms appear to stem from the metabolic inflexibility imposed by insulin resistance or lack of insulin signaling. This results in absolute reliance on fatty acids for the synthesis of ATP and impairment of glucose oxidation. Glucose is then rerouted to other metabolic pathways, with harmful effects on cardiomyocyte function. Here, we discuss the role that impaired cardiac insulin signaling in diabetic or insulin-resistant individuals plays in the onset and progression of DCM. Keywords: insulin resistance; diabetes; heart; diabetic cardiomyopathy; metabolic flexibility Author: Mònica Zamora and Josep A. 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false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: ぅばどつづねどはぬはでべぜ〴ぜ〰ちのつぜ〴ぜ〰ぐちぴとはばとべびどはぬはでべぜ〴ぜ〰はてぜ〴ぜ〰いぃきぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぉのびふぬどのぜ〴ぜ〰げづびどびぴちのっづぜ〴ぜ〰ちのつぜ〴ぜ〰ぴとづぜ〴ぜ〰ぐちぴとはでづのづびどびぜ〴ぜ〰はてぜ〴ぜ〰いぃきぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰きはぬづっふぬちひぜ〴ぜ〰ちのつぜ〴ぜ〰ぃづぬぬふぬちひぜ〴ぜ〰きづっとちのどびねびぜ〴ぜ〰はてぜ〴ぜ〰いぃきぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸱ Children: Item: Title: きはぬづっふぬちひぜ〴ぜ〰ちのつぜ〴ぜ〰ぃづぬぬふぬちひぜ〴ぜ〰きづっとちのどびねびぜ〴ぜ〰はてぜ〴ぜ〰いぃきぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸱ Children: Item: Title: ぉのっひづちびづつぜ〴ぜ〰ぐひはつふっぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぁぇぅびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸲ Item: Title: ぉのっひづちびづつぜ〴ぜ〰こふぢびぴひちぴづぜ〴ぜ〰うぬふへぜ〴ぜ〰ぴとひはふでとぜ〴ぜ〰ぴとづぜ〴ぜ〰えづへはびちねどのづぜ〴ぜ〰あどはびべのぴとづぴどっぜ〴ぜ〰ぐちぴとぷちべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸳ Item: Title: がどばはぴはへどっどぴべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸴ Item: Title: げくこぜ〴ぜ〰ぐひはつふっぴどはのぜ〴ぜ〰ちのつぜ〴ぜ〰きどぴはっとはのつひどちぬぜ〴ぜ〰いべびてふのっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸵ Item: Title: ぁっぴどぶちぴどはのぜ〴ぜ〰はてぜ〴ぜ〰げぁこぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獵扳散瑩潮⸳⸱⸶ Item: Title: ぃちぬっどふねぜ〴ぜ〰きどびとちのつぬどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰ぅててづっぴびぜ〴ぜ〰はてぜ〴ぜ〰ぉのびふぬどのぜ〴ぜ〰げづびどびぴちのっづぜ〴ぜ〰はのぜ〴ぜ〰きづぴちぢはぬどっぜ〴ぜ〰うぬづへどぢどぬどぴべぜ〴ぜ〰ちのつぜ〴ぜ〰どぴびぜ〴ぜ〰ぉねばぬどっちぴどはのびぜ〴ぜ〰はのぜ〴ぜ〰ぃちひつどちっぜ〴ぜ〰いべびてふのっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぅててづっぴびぜ〴ぜ〰はてぜ〴ぜ〰ぉのびふぬどのぜ〴ぜ〰げづびどびぴちのっづぜ〴ぜ〰はのぜ〴ぜ〰きづぴちぢはぬどっぜ〴ぜ〰うぬづへどぢどぬどぴべぜ〴ぜ〰ちのつぜ〴ぜ〰どぴびぜ〴ぜ〰ぉねばぬどっちぴどはのびぜ〴ぜ〰はのぜ〴ぜ〰ぃちひつどちっぜ〴ぜ〰いべびてふのっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: げはつづのぴぜ〴ぜ〰きはつづぬびぜ〴ぜ〰はてぜ〴ぜ〰ぉねばちどひづつぜ〴ぜ〰ぉのびふぬどのぜ〴ぜ〰こどでのちぬどのでぜ〴ぜ〰てはひぜ〴ぜ〰ぴとづぜ〴ぜ〰こぴふつべぜ〴ぜ〰はてぜ〴ぜ〰いぃきぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぇづのづぴどっぜ〴ぜ〰きはつづぬびぜ〴ぜ〰はてぜ〴ぜ〰ぃちひつどちっ〭こばづっどてどっぜ〴ぜ〰いどびひふばぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぉのびふぬどのぜ〴ぜ〰こどでのちぬどのでぜ〴ぜ〰てはひぜ〴ぜ〰ぴとづぜ〴ぜ〰こぴふつべぜ〴ぜ〰はてぜ〴ぜ〰いぃきぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰げはつづのぴぜ〴ぜ〰きはつづぬびぜ〴ぜ〰はてぜ〴ぜ〰いどちぢづぴづびぜ〴ぜ〰はひぜ〴ぜ〰こべびぴづねどっぜ〴ぜ〰ぉのびふぬどのぜ〴ぜ〰げづびどびぴちのっづぜ〴ぜ〰てはひぜ〴ぜ〰ぴとづぜ〴ぜ〰こぴふつべぜ〴ぜ〰はてぜ〴ぜ〰いぃきぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Children: Item: Title: ぇづのづぴどっぜ〴ぜ〰きはつづぬびぜ〴ぜ〰はてぜ〴ぜ〰ぃちひつどちっ〭こばづっどてどっぜ〴ぜ〰いどびひふばぴどはのぜ〴ぜ〰はてぜ〴ぜ〰ぉのびふぬどのぜ〴ぜ〰こどでのちぬどのでぜ〴ぜ〰てはひぜ〴ぜ〰ぴとづぜ〴ぜ〰こぴふつべぜ〴ぜ〰はてぜ〴ぜ〰いぃきぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㐮㈩‾㸊⡜㌷㙜㌷㝜〰げはつづのぴぜ〴ぜ〰きはつづぬびぜ〴ぜ〰はてぜ〴ぜ〰いどちぢづぴづびぜ〴ぜ〰はひぜ〴ぜ〰こべびぴづねどっぜ〴ぜ〰ぉのびふぬどのぜ〴ぜ〰げづびどびぴちのっづぜ〴ぜ〰てはひぜ〴ぜ〰ぴとづぜ〴ぜ〰こぴふつべぜ〴ぜ〰はてぜ〴ぜ〰いぃきぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: げはつづのぴぜ〴ぜ〰きはつづぬびぜ〴ぜ〰はてぜ〴ぜ〰いどちぢづぴづびぜ〴ぜ〰はひぜ〴ぜ〰こべびぴづねどっぜ〴ぜ〰ぉのびふぬどのぜ〴ぜ〰げづびどびぴちのっづぜ〴ぜ〰てはひぜ〴ぜ〰ぴとづぜ〴ぜ〰こぴふつべぜ〴ぜ〰はてぜ〴ぜ〰いぃきぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: VSHNAE+Rpcxr FontSubset: true FirstChar: 169 LastChar: 169 FontDescriptor: FontName: VSHNAE+Rpcxr Flags: Symbolic FontBBox: -212, -286, 1344, 973 FontFile: true Font: BaseFont: USSQAS+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 121 FontDescriptor: FontName: USSQAS+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: LEBGPB+URWPalladioL-Bold 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