Entry
Name
Diabetic cardiomyopathy - Homo sapiens (human)
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
Disease
H02498 Diabetic cardiomyopathy
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
10476 ATP5PD; ATP synthase peripheral stalk subunit d [KO:K02138 ]
10975 UQCR11; ubiquinol-cytochrome c reductase, complex III subunit XI [KO:K00420 ]
126328 NDUFA11; NADH:ubiquinone oxidoreductase subunit A11 [KO:K03956 ]
1277 COL1A1; collagen type I alpha 1 chain [KO:K06236 ]
1278 COL1A2; collagen type I alpha 2 chain [KO:K06236 ]
1281 COL3A1; collagen type III alpha 1 chain [KO:K19720 ]
1327 COX4I1; cytochrome c oxidase subunit 4I1 [KO:K02263 ]
1329 COX5B; cytochrome c oxidase subunit 5B [KO:K02265 ]
1337 COX6A1; cytochrome c oxidase subunit 6A1 [KO:K02266 ]
1339 COX6A2; cytochrome c oxidase subunit 6A2 [KO:K02266 ]
1340 COX6B1; cytochrome c oxidase subunit 6B1 [KO:K02267 ]
1345 COX6C; cytochrome c oxidase subunit 6C [KO:K02268 ]
1346 COX7A1; cytochrome c oxidase subunit 7A1 [KO:K02270 ]
1347 COX7A2; cytochrome c oxidase subunit 7A2 [KO:K02270 ]
1349 COX7B; cytochrome c oxidase subunit 7B [KO:K02271 ]
1350 COX7C; cytochrome c oxidase subunit 7C [KO:K02272 ]
1351 COX8A; cytochrome c oxidase subunit 8A [KO:K02273 ]
142 PARP1; poly(ADP-ribose) polymerase 1 [KO:K24070 ]
1535 CYBA; cytochrome b-245 alpha chain [KO:K08009 ]
1536 CYBB; cytochrome b-245 beta chain [KO:K21421 ] [EC:1.-.-.-]
177 AGER; advanced glycosylation end-product specific receptor [KO:K19722 ]
185 AGTR1; angiotensin II receptor type 1 [KO:K04166 ]
25874 MPC2; mitochondrial pyruvate carrier 2 [KO:K22139 ]
27089 UQCRQ; ubiquinol-cytochrome c reductase complex III subunit VII [KO:K00418 ]
291 SLC25A4; solute carrier family 25 member 4 [KO:K05863 ]
292 SLC25A5; solute carrier family 25 member 5 [KO:K05863 ]
293 SLC25A6; solute carrier family 25 member 6 [KO:K05863 ]
29796 UQCR10; ubiquinol-cytochrome c reductase, complex III subunit X [KO:K00419 ]
347411 MPC1L; mitochondrial pyruvate carrier 1 like [KO:K22138 ]
3667 IRS1; insulin receptor substrate 1 [KO:K16172 ]
440567 UQCRHL; ubiquinol-cytochrome c reductase hinge protein like [KO:K00416 ]
4513 COX2; cytochrome c oxidase subunit II [KO:K02261 ]
4514 COX3; cytochrome c oxidase subunit III [KO:K02262 ]
4688 NCF2; neutrophil cytosolic factor 2 [KO:K08010 ]
4689 NCF4; neutrophil cytosolic factor 4 [KO:K08012 ]
4694 NDUFA1; NADH:ubiquinone oxidoreductase subunit A1 [KO:K03945 ]
4695 NDUFA2; NADH:ubiquinone oxidoreductase subunit A2 [KO:K03946 ]
4696 NDUFA3; NADH:ubiquinone oxidoreductase subunit A3 [KO:K03947 ]
4697 NDUFA4; NDUFA4 mitochondrial complex associated [KO:K03948 ]
4698 NDUFA5; NADH:ubiquinone oxidoreductase subunit A5 [KO:K03949 ]
4700 NDUFA6; NADH:ubiquinone oxidoreductase subunit A6 [KO:K03950 ]
4701 NDUFA7; NADH:ubiquinone oxidoreductase subunit A7 [KO:K03951 ]
4702 NDUFA8; NADH:ubiquinone oxidoreductase subunit A8 [KO:K03952 ]
4704 NDUFA9; NADH:ubiquinone oxidoreductase subunit A9 [KO:K03953 ]
4705 NDUFA10; NADH:ubiquinone oxidoreductase subunit A10 [KO:K03954 ]
4706 NDUFAB1; NADH:ubiquinone oxidoreductase subunit AB1 [KO:K03955 ]
4707 NDUFB1; NADH:ubiquinone oxidoreductase subunit B1 [KO:K03957 ]
4708 NDUFB2; NADH:ubiquinone oxidoreductase subunit B2 [KO:K03958 ]
4709 NDUFB3; NADH:ubiquinone oxidoreductase subunit B3 [KO:K03959 ]
4710 NDUFB4; NADH:ubiquinone oxidoreductase subunit B4 [KO:K03960 ]
4711 NDUFB5; NADH:ubiquinone oxidoreductase subunit B5 [KO:K03961 ]
4712 NDUFB6; NADH:ubiquinone oxidoreductase subunit B6 [KO:K03962 ]
4713 NDUFB7; NADH:ubiquinone oxidoreductase subunit B7 [KO:K03963 ]
4714 NDUFB8; NADH:ubiquinone oxidoreductase subunit B8 [KO:K03964 ]
4715 NDUFB9; NADH:ubiquinone oxidoreductase subunit B9 [KO:K03965 ]
4716 NDUFB10; NADH:ubiquinone oxidoreductase subunit B10 [KO:K03966 ]
4717 NDUFC1; NADH:ubiquinone oxidoreductase subunit C1 [KO:K03967 ]
4718 NDUFC2; NADH:ubiquinone oxidoreductase subunit C2 [KO:K03968 ]
4724 NDUFS4; NADH:ubiquinone oxidoreductase subunit S4 [KO:K03937 ]
4725 NDUFS5; NADH:ubiquinone oxidoreductase subunit S5 [KO:K03938 ]
4726 NDUFS6; NADH:ubiquinone oxidoreductase subunit S6 [KO:K03939 ]
4731 NDUFV3; NADH:ubiquinone oxidoreductase subunit V3 [KO:K03944 ]
4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580 ]
487 ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853 ] [EC:7.2.2.10 ]
488 ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853 ] [EC:7.2.2.10 ]
489 ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853 ] [EC:7.2.2.10 ]
498 ATP5F1A; ATP synthase F1 subunit alpha [KO:K02132 ]
509 ATP5F1C; ATP synthase F1 subunit gamma [KO:K02136 ]
51079 NDUFA13; NADH:ubiquinone oxidoreductase subunit A13 [KO:K11353 ]
513 ATP5F1D; ATP synthase F1 subunit delta [KO:K02134 ]
514 ATP5F1E; ATP synthase F1 subunit epsilon [KO:K02135 ]
515 ATP5PB; ATP synthase peripheral stalk-membrane subunit b [KO:K02127 ]
516 ATP5MC1; ATP synthase membrane subunit c locus 1 [KO:K02128 ]
51660 MPC1; mitochondrial pyruvate carrier 1 [KO:K22138 ]
517 ATP5MC2; ATP synthase membrane subunit c locus 2 [KO:K02128 ]
518 ATP5MC3; ATP synthase membrane subunit c locus 3 [KO:K02128 ]
522 ATP5PF; ATP synthase peripheral stalk subunit F6 [KO:K02131 ]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
539 ATP5PO; ATP synthase peripheral stalk subunit OSCP [KO:K02137 ]
54539 NDUFB11; NADH:ubiquinone oxidoreductase subunit B11 [KO:K11351 ]
5465 PPARA; peroxisome proliferator activated receptor alpha [KO:K07294 ]
5524 PTPA; protein phosphatase 2 phosphatase activator [KO:K17605 ]
55967 NDUFA12; NADH:ubiquinone oxidoreductase subunit A12 [KO:K11352 ]
56901 NDUFA4L2; NDUFA4 mitochondrial complex associated like 2 [KO:K03948 ]
5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735 ]
6389 SDHA; succinate dehydrogenase complex flavoprotein subunit A [KO:K00234 ] [EC:1.3.5.1 ]
6390 SDHB; succinate dehydrogenase complex iron sulfur subunit B [KO:K00235 ] [EC:1.3.5.1 ]
6391 SDHC; succinate dehydrogenase complex subunit C [KO:K00236 ]
6392 SDHD; succinate dehydrogenase complex subunit D [KO:K00237 ]
6513 SLC2A1; solute carrier family 2 member 1 [KO:K07299 ]
6517 SLC2A4; solute carrier family 2 member 4 [KO:K07191 ]
7040 TGFB1; transforming growth factor beta 1 [KO:K13375 ]
7042 TGFB2; transforming growth factor beta 2 [KO:K13376 ]
7043 TGFB3; transforming growth factor beta 3 [KO:K13377 ]
7381 UQCRB; ubiquinol-cytochrome c reductase binding protein [KO:K00417 ]
7384 UQCRC1; ubiquinol-cytochrome c reductase core protein 1 [KO:K00414 ]
7385 UQCRC2; ubiquinol-cytochrome c reductase core protein 2 [KO:K00415 ]
7386 UQCRFS1; ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 [KO:K00411 ] [EC:7.1.1.8 ]
7388 UQCRH; ubiquinol-cytochrome c reductase hinge protein [KO:K00416 ]
7416 VDAC1; voltage dependent anion channel 1 [KO:K05862 ]
7417 VDAC2; voltage dependent anion channel 2 [KO:K15040 ]
7419 VDAC3; voltage dependent anion channel 3 [KO:K15041 ]
815 CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515 ] [EC:2.7.11.17 ]
816 CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515 ] [EC:2.7.11.17 ]
817 CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515 ] [EC:2.7.11.17 ]
818 CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515 ] [EC:2.7.11.17 ]
83447 SLC25A31; solute carrier family 25 member 31 [KO:K05863 ]
84701 COX4I2; cytochrome c oxidase subunit 4I2 [KO:K02263 ]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
9167 COX7A2L; cytochrome c oxidase subunit 7A2 like [KO:K02270 ]
9377 COX5A; cytochrome c oxidase subunit 5A [KO:K02264 ]
948 CD36; CD36 molecule (CD36 blood group) [KO:K06259 ]
9882 TBC1D4; TBC1 domain family member 4 [KO:K17902 ]
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
hsa00520 Amino sugar and nucleotide sugar metabolism
hsa04933 AGE-RAGE signaling pathway in diabetic complications
KO pathway