Altered myocardial substrate metabolism is associated with myocardial dysfunction in early diabetic cardiomyopathy in rats: studies using positron emission tomography

Brom, Charissa E. van den; Huisman, Marc C.; Vlasblom, Ronald; Boontje, Nicky M.; Duijst, Suzanne; Lubberink, Mark; Molthoff, Carla F. M.; Lammertsma, Adriaan A.; Velden, Jolanda van der; Boer, Christa; Ouwens, D. Margriet; Diamant, Michaëla

doi:10.1186/1475-2840-8-39

Cited by 107 publications

(113 citation statements)

References 36 publications

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“…In contrast, the stimulated recruitment of GLUT4 would not be initially impaired and its dysfunction would occur later as a result of abnormal FA metabolism. This interpretation is consistent with earlier fi ndings documenting that the aberrant CD36 traffi cking in an insulin-resistant state develops before the dysregulation of GLUT4 traffi cking ( 5,(12)(13)(14).…”

Section: Uncoupling Of Glut4 and Cd36 Membrane Recruitment In The Inssupporting

confidence: 81%

“…Six hours later, the medium was changed to fully evidenced from fi ndings under conditions in which it is dysregulated. For example, persistent relocation of CD36 from intracellular stores to the sarcolemma is observed in the diabetic myocardium and is proposed to result in accumulation of lipid moieties with negative effects on heart metabolism and function ( 1,5,(12)(13)(14). The permanent relocation of CD36 to the plasma membrane is an early event in insulin resistance that precedes and strongly correlates with intracellular retention of the insulinsensitive glucose transporter GLUT4 ( 2 ).…”

Section: Rna Interference (Rnai)-mediated Silencingmentioning

confidence: 99%

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Insulin and AMPK regulate FA translocase/CD36 plasma membrane recruitment in cardiomyocytes via Rab GAP AS160 and Rab8a Rab GTPase

Samovski

et al. 2012

Journal of Lipid Research

108

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regulated by multiple factors, including insulin and contraction ( 1, 2 ). Several proteins have been proposed to facilitate FA uptake by the myocardium, and these include the scavenger receptor cluster of differentiation 36 (CD36), the FA transport proteins, caveolin1, and plasma membrane-associated FA binding protein (as reviewed in Ref. 1 ). In addition to these proteins, acyl-CoA ligases that activate FA by generating the FA acyl-CoA, couple FA entry to metabolism and help maintain the gradient for FA infl ux across the plasma membrane ( 1,3 ) CD36 is abundantly expressed in the heart and facilitates a signifi cant part of myocardial FA uptake measured in vivo in humans and rodents ( 4, 5 ). Unlike other proteins implicated in FA uptake, CD36 cycles between intracellular stores and the plasma membrane, similar to the glucose transporter GLUT4. CD36 traffi cking is regulated by a number of factors including insulin, muscle contraction ( 1, 2 ), purinergic agonists such as uridine-5 ′ -triphosphate (UTP) ( 6 ), and FAs ( 7-9 ). It is believed that the effect of muscle contraction on CD36 surface translocation is mediated via activation of AMP-dependent protein kinase (AMPK) ( 10 ), although this notion was recently challenged in skeletal muscle ( 11 ).Insulin and contraction increase CD36 surface expression on cardiomyocytes to enhance myocardial extraction of circulating FA. The internalized FA is either directly oxidized in mitochondria (AMPK and contraction) or partitioned fi rst into triglycerides (insulin) that can later be hydrolyzed to provide FA for oxidation (as reviewed in Ref. Press, February 6, 2012 DOI 10.1194 Abbreviations: AICAR, 5-aminoimidazole-4-carboxamide-1-beta-Dribofuranoside; AMPK, AMP-dependent protein kinase; AS160, Akt substrate 160; CA, constitutively active; CD36, fatty acid translocase cluster of differentiation 36; CHO, Chinese hamster ovary; DN, dominant-negative; GAP, GTPase-activating protein; GEF, guanine exchange factor; GFP, green fl uorescent protein; RNAi, RNA interference; siRNA, small interfering RNA; UTP, uridine-5 ′ -triphosphate; Wt, wild-type. Published, JLR Papers in

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Section: Uncoupling Of Glut4 and Cd36 Membrane Recruitment In The Inssupporting

confidence: 81%

Section: Rna Interference (Rnai)-mediated Silencingmentioning

confidence: 99%

Insulin and AMPK regulate FA translocase/CD36 plasma membrane recruitment in cardiomyocytes via Rab GAP AS160 and Rab8a Rab GTPase

Samovski

et al. 2012

Journal of Lipid Research

108

View full text Add to dashboard Cite

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“…23 ZDF sıçanlarda 12-14. haftalarda diyastolik ve sistolik disfonksiyon ile hiperinsülinemi ve 13-15. haftalarda hipertrigliseridemi ile hiperglisemi oluş-maktadır. 24,25 Bu sıçanlarda ayrıca, 12. haftadan sonra endotel fonksiyon bozukluğu ve 15. haftada sistolik kan basıncında orta dereceli artış görül-mektedir. 19,[23][24][25] Albuminüri, 47. haftadan sonra şekillenen bazal membranın kalınlaşması ve glomerüler fibroz ile birlikte görülmektedir.…”

Section: Zucker Diyabetik Yağlı Sıçan (Zdf) Metabolik Sendrom Modeliunclassified

“…24,25 Bu sıçanlarda ayrıca, 12. haftadan sonra endotel fonksiyon bozukluğu ve 15. haftada sistolik kan basıncında orta dereceli artış görül-mektedir. 19,[23][24][25] Albuminüri, 47. haftadan sonra şekillenen bazal membranın kalınlaşması ve glomerüler fibroz ile birlikte görülmektedir. ZDF sı-çanlarda, 26. haftadan sonra tümör nekrozis faktör alfa (TNF-α) ve interlökin (IL)-1β gibi inflamasyon belirteçleri serumda artış göstermektedir.…”

Section: Zucker Diyabetik Yağlı Sıçan (Zdf) Metabolik Sendrom Modeliunclassified

Metabolic Syndrome and Diabetic Experimental Animal Models

Çelik¹,

Haliloğlu²

2017

Turkiye Klinikleri J Lab Anim

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“…The net result of enhanced fatty acid oxidation and decreased glucose and pyruvate utilization led to the excess of glycolytic intermediates and increased the synthesis of ceramide leading to apoptosis. This process, called gluco-lipotoxicity induced mitochondrial uncoupling, decreased adenosine triphosphate synthesis and mitochondrial dysfunction [20,21] . Changes in substrate dependence lead to impaired systolic and diastolic function due to the perturbation of myocardial bioenergetics and contraction/relaxation coupling [21,22] .…”

Section: Altered Substrate Metabolismmentioning

confidence: 99%

Is diabetic cardiomyopathy a specific entity?

Letonja

Petrovič

2014

WJC

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Diabetes mellitus (DM) is characterised by hyperglycemia, insulin resistance and metabolic dysregulation leading to diastolic and systolic dysfunction in diabetes. In this review, the pathogenetic and pathomorphological changes leading to diastolic and systolic dysfunction in diabetes are discussed. Changes in metabolic signalling pathways, mediators and effectors contribute to the pathogenesis of cardiac dysfunction in DM called diabetic cardiomyopathy (DC). Echocardiographic studies report on the association between DM and the presence of cardiac hypertrophy and myocardial stiffness that lead to diastolic dysfunction. More recently reported echocardiographic studies with more sensitive techniques, such as strain analysis, also observed systolic dysfunction as an early marker of DC. Depression of systolic and diastolic function is continuum and the line of separation is artificial. To conclude, according to current knowledge, DC is expected to be a common single phenotype that is caused by different pathogenetic and pathomorphological changes leading to diastolic and systolic dysfunction in diabetes.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Diabetes mellitus; Diabetic cardiomyopathy; Pathogenesis; Diastolic dysfunction; Systolic dysfunction; Morphological changes; Apoptosis Core tip: Changes in metabolic signalling pathways via several mediators contribute to the pathogenesis of cardiac dysfunction in diabetes called diabetic cardiomyopathy (DC). In this review, the pathogenetic and pathomorphological changes leading to diastolic and systolic dysfunction in diabetes are discussed. Echocardiographic studies report on the association between diabetes and the presence of cardiac hypertrophy and myocardial stiffness that lead to diastolic dysfunction. More recently reported echocardiographic studies with more sensitive techniques, such as strain analysis, also observed systolic dysfunction as an early marker of DC.Letonja M, Petrovič D. Is diabetic cardiomyopathy a specific entity? World J Cardiol 2014; 6(1): 8-13 Available from: URL:

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Altered myocardial substrate metabolism is associated with myocardial dysfunction in early diabetic cardiomyopathy in rats: studies using positron emission tomography

Cited by 107 publications

References 36 publications

Insulin and AMPK regulate FA translocase/CD36 plasma membrane recruitment in cardiomyocytes via Rab GAP AS160 and Rab8a Rab GTPase

Insulin and AMPK regulate FA translocase/CD36 plasma membrane recruitment in cardiomyocytes via Rab GAP AS160 and Rab8a Rab GTPase

Metabolic Syndrome and Diabetic Experimental Animal Models

Is diabetic cardiomyopathy a specific entity?

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