Entry
Name
Diabetic cardiomyopathy - Enhydra lutris kenyoni (northern sea otter)
Description
Diabetic cardiomyopathy has been defined as left ventricular dysfunction that occurs among patients with diabetes mellitus independent of a recognized cause such as coronary artery disease or hypertension. The pathogenesis of diabetic cardiomyopathy broadly involves hyperglycemia, increased circulating fatty acids, and insulin resistance contributing to reactive oxygen species (ROS) generation, mitochondrial dysfunction, impaired calcium metabolism, Renin-Angiotensin System (RAS) activation, and altered substrate metabolism. These effects result in cardiac fibrosis, hypertrophy, cardiomyocyte death, contractile dysfunction, endothelial cell damage and eventually heart failure. In the process of cardiac fibrosis, cardiac fibroblasts are the final effector cell.
Class
Human Diseases; Cardiovascular disease
BRITE hierarchy
Pathway map
Ortholog table
Organism
Enhydra lutris kenyoni (northern sea otter) [GN:
elk ]
Gene
111143335 solute carrier family 2, facilitated glucose transporter member 1 isoform X1 [KO:K07299 ]
111161132 solute carrier family 2, facilitated glucose transporter member 4 isoform X1 [KO:K07191 ]
111152179 advanced glycosylation end product-specific receptor isoform X1 [KO:K19722 ]
111145636 ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
111145946 serine/threonine-protein phosphatase 2A activator isoform X1 [KO:K17605 ]
111144767 LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269 ] [EC:3.1.3.16 ]
111155003 LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
111154641 phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
111143470 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
111155224 phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
111143790 phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
111150409 pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform X1 [KO:K00161 ] [EC:1.2.4.1 ]
111157464 pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial [KO:K00161 ] [EC:1.2.4.1 ]
111155738 NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial isoform X1 [KO:K03944 ]
111157253 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 [KO:K03945 ]
111140937 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 [KO:K03946 ]
111139570 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 [KO:K03947 ]
111152555 LOW QUALITY PROTEIN: cytochrome c oxidase subunit NDUFA4-like [KO:K03948 ]
111160211 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2 [KO:K03948 ]
111154239 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5-like isoform X1 [KO:K03949 ]
111151938 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 isoform X1 [KO:K03949 ]
111155596 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5-like [KO:K03949 ]
111157547 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 isoform X1 [KO:K03950 ]
111161756 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7 [KO:K03951 ]
111145557 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 [KO:K03952 ]
111159811 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial [KO:K03953 ]
111161328 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial [KO:K03954 ]
111161769 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 [KO:K03956 ]
111142148 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 isoform X1 [KO:K11352 ]
111143867 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 [KO:K11353 ]
111148723 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1 [KO:K03957 ]
111151936 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial [KO:K03958 ]
111141342 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 [KO:K03959 ]
111148802 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4 isoform X1 [KO:K03960 ]
111147306 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mitochondrial isoform X1 [KO:K03961 ]
111146284 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6 isoform X1 [KO:K03962 ]
111162542 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7 [KO:K03963 ]
111145242 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial isoform X1 [KO:K03964 ]
111146716 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 isoform X1 [KO:K03965 ]
111156034 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 [KO:K03966 ]
111150594 NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial [KO:K11351 ]
111141116 NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial [KO:K03937 ]
111142993 NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 [KO:K03938 ]
111153450 NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial [KO:K03939 ]
111149131 NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial [KO:K03967 ]
111154340 NADH dehydrogenase [ubiquinone] 1 subunit C2 isoform X1 [KO:K03968 ]
111153400 succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial isoform X1 [KO:K00234 ] [EC:1.3.5.1 ]
111154638 succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial isoform X1 [KO:K00235 ] [EC:1.3.5.1 ]
111138865 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform X1 [KO:K00236 ]
111153893 succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial isoform X1 [KO:K00237 ]
111143869 cytochrome b-c1 complex subunit 1, mitochondrial isoform X1 [KO:K00414 ]
111142816 cytochrome b-c1 complex subunit 6, mitochondrial isoform X1 [KO:K00416 ]
111153043 cytochrome c oxidase subunit 4 isoform 1, mitochondrial [KO:K02263 ]
111141707 cytochrome c oxidase subunit 4 isoform 2, mitochondrial isoform X1 [KO:K02263 ]
111155858 cytochrome c oxidase subunit 5B, mitochondrial isoform X1 [KO:K02265 ]
111156401 cytochrome c oxidase subunit 6A1, mitochondrial isoform X1 [KO:K02266 ]
111158437 cytochrome c oxidase subunit 7A-related protein, mitochondrial isoform X1 [KO:K02270 ]
111160948 LOW QUALITY PROTEIN: cytochrome c oxidase subunit 8A, mitochondrial-like [KO:K02273 ]
111151344 ATP synthase F(0) complex subunit C1, mitochondrial isoform X1 [KO:K02128 ]
111151840 ATP synthase-coupling factor 6, mitochondrial isoform X1 [KO:K02131 ]
111141207 voltage-dependent anion-selective channel protein 1 isoform X1 [KO:K05862 ]
111144425 voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041 ]
Compound
C00043 UDP-N-acetyl-alpha-D-glucosamine
C00118 D-Glyceraldehyde 3-phosphate
C00236 3-Phospho-D-glyceroyl phosphate
C00352 D-Glucosamine 6-phosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
C06156 alpha-D-Glucosamine 1-phosphate
C21011 [Protein]-N(epsilon)-(carboxymethyl)lysine
C21012 [Protein]-N(epsilon)-(carboxyethyl)lysine
Reference
Authors
Riehle C, Bauersachs J
Title
Of mice and men: models and mechanisms of diabetic cardiomyopathy.
Journal
Reference
Authors
Huynh K, Bernardo BC, McMullen JR, Ritchie RH
Title
Diabetic cardiomyopathy: mechanisms and new treatment strategies targeting antioxidant signaling pathways.
Journal
Reference
Authors
Lorenzo-Almoros A, Tunon J, Orejas M, Cortes M, Egido J, Lorenzo O
Title
Diagnostic approaches for diabetic cardiomyopathy.
Journal
Reference
Authors
Tan Y, Zhang Z, Zheng C, Wintergerst KA, Keller BB, Cai L
Title
Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence.
Journal
Reference
Authors
Zamora M, Villena JA
Title
Contribution of Impaired Insulin Signaling to the Pathogenesis of Diabetic Cardiomyopathy.
Journal
Reference
Authors
Palomer X, Pizarro-Delgado J, Vazquez-Carrera M
Title
Emerging Actors in Diabetic Cardiomyopathy: Heartbreaker Biomarkers or Therapeutic Targets?
Journal
Reference
Authors
Mishra PK, Ying W, Nandi SS, Bandyopadhyay GK, Patel KK, Mahata SK
Title
Diabetic Cardiomyopathy: An Immunometabolic Perspective.
Journal
Reference
Authors
Chong CR, Clarke K, Levelt E
Title
Metabolic Remodeling in Diabetic Cardiomyopathy.
Journal
Reference
Authors
Brownlee M
Title
Biochemistry and molecular cell biology of diabetic complications.
Journal
Reference
Authors
Gollmer J, Zirlik A, Bugger H
Title
Established and Emerging Mechanisms of Diabetic Cardiomyopathy.
Journal
Reference
Authors
Boudina S, Abel ED
Title
Diabetic cardiomyopathy revisited.
Journal
Reference
Authors
Varma U, Koutsifeli P, Benson VL, Mellor KM, Delbridge LMD
Title
Molecular mechanisms of cardiac pathology in diabetes - Experimental insights.
Journal
Reference
Authors
Mandavia CH, Aroor AR, Demarco VG, Sowers JR
Title
Molecular and metabolic mechanisms of cardiac dysfunction in diabetes.
Journal
Reference
Authors
Falcao-Pires I, Leite-Moreira AF
Title
Diabetic cardiomyopathy: understanding the molecular and cellular basis to progress in diagnosis and treatment.
Journal
Reference
Authors
Westermeier F, Riquelme JA, Pavez M, Garrido V, Diaz A, Verdejo HE, Castro PF, Garcia L, Lavandero S
Title
New Molecular Insights of Insulin in Diabetic Cardiomyopathy.
Journal
Reference
Authors
Randhawa VK, Dhanvantari S, Connelly K
Title
How Diabetes and Heart Failure Modulate Each Other and Condition Management.
Journal
Reference
Authors
Athithan L, Gulsin GS, McCann GP, Levelt E
Title
Diabetic cardiomyopathy: Pathophysiology, theories and evidence to date.
Journal
Reference
Authors
Murarka S, Movahed MR
Title
Diabetic cardiomyopathy.
Journal
Reference
Authors
Thomas CM, Yong QC, Rosa RM, Seqqat R, Gopal S, Casarini DE, Jones WK, Gupta S, Baker KM, Kumar R
Title
Cardiac-specific suppression of NF-kappaB signaling prevents diabetic cardiomyopathy via inhibition of the renin-angiotensin system.
Journal
Reference
Authors
Brahma MK, Pepin ME, Wende AR
Title
My Sweetheart Is Broken: Role of Glucose in Diabetic Cardiomyopathy.
Journal
Reference
Authors
Singh VP, Le B, Khode R, Baker KM, Kumar R
Title
Intracellular angiotensin II production in diabetic rats is correlated with cardiomyocyte apoptosis, oxidative stress, and cardiac fibrosis.
Journal
Reference
Authors
Singh VP, Baker KM, Kumar R
Title
Activation of the intracellular renin-angiotensin system in cardiac fibroblasts by high glucose: role in extracellular matrix production.
Journal
Reference
Authors
Jia G, DeMarco VG, Sowers JR
Title
Insulin resistance and hyperinsulinaemia in diabetic cardiomyopathy.
Journal
Reference
Authors
Kim JA, Wei Y, Sowers JR
Title
Role of mitochondrial dysfunction in insulin resistance.
Journal
Reference
Authors
Ormazabal V, Nair S, Elfeky O, Aguayo C, Salomon C, Zuniga FA
Title
Association between insulin resistance and the development of cardiovascular disease.
Journal
Reference
Authors
Evangelista I, Nuti R, Picchioni T, Dotta F, Palazzuoli A
Title
Molecular Dysfunction and Phenotypic Derangement in Diabetic Cardiomyopathy.
Journal
Reference
Authors
Joshi M, Kotha SR, Malireddy S, Selvaraju V, Satoskar AR, Palesty A, McFadden DW, Parinandi NL, Maulik N
Title
Conundrum of pathogenesis of diabetic cardiomyopathy: role of vascular endothelial dysfunction, reactive oxygen species, and mitochondria.
Journal
Reference
Authors
Knapp M, Tu X, Wu R
Title
Vascular endothelial dysfunction, a major mediator in diabetic cardiomyopathy.
Journal
Reference
Authors
Asbun J, Villarreal FJ
Title
The pathogenesis of myocardial fibrosis in the setting of diabetic cardiomyopathy.
Journal
Reference
Authors
Levick SP, Widiapradja A
Title
The Diabetic Cardiac Fibroblast: Mechanisms Underlying Phenotype and Function.
Journal
Related pathway
elk00520 Amino sugar and nucleotide sugar metabolism
elk04933 AGE-RAGE signaling pathway in diabetic complications
KO pathway
LinkDB
All DBs