ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2012
Excess protein O-GlcNAcylation and the progression of diabetic cardiomyopathy.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 104 citations in OpenAlex.
- Cardiac Lipid Metabolism: Cells, Metabolites, and Rhythms.Circulation research · 2026Review
- The Landscape of SERCA2 in Cardiovascular Diseases: Expression Regulation, Therapeutic Applications, and Emerging Roles.Biomolecules · 2026Review
- Glutamine: fructose-6-phosphate amidotransferase (GFAT) in the pathology of diseases: a review.Cell death discovery · 2025Review
- Allosteric Modulation of SERCA Pumps in Health and Disease: Structural Dynamics, Posttranslational Modifications, and Therapeutic Potential.Journal of molecular biology · 2025Review
- Guidelines for diet-induced models of cardiometabolic syndrome.American journal of physiology. Heart and circulatory physiology · 2025Review
- Metabolic and Mitochondrial Dysregulations in Diabetic Cardiac Complications.International journal of molecular sciences · 2025Review
- Anaplerotic filling in heart failure: a review of mechanism and potential therapeutics.Cardiovascular research · 2024Review
- The post-translational modification O-GlcNAc is a sensor and regulator of metabolism.Open biology · 2024Review
- Roles of O-GlcNAcylation in Mitochondrial Homeostasis and Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Molecular mechanisms of metabolic dysregulation in diabetic cardiomyopathy.Frontiers in cardiovascular medicine · 2024Review
- Deletion of Smooth Muscle O-GlcNAc Transferase Prevents Development of Atherosclerosis in Western Diet-Fed Hyperglycemic ApoEInternational journal of molecular sciences · 2023Article
- Transient receptor potential canonical type 6 (TRPC6) O-GlcNAcylation at Threonine-221 plays potent role in channel regulation.iScience · 2023Article
- High Dose of Metformin Decreases Susceptibility to Occlusive Arterial Thrombosis in Diabetic Mice.Journal of pharmacy and pharmacology research · 2023Article
- Exercise improves angiogenic function of circulating exosomes in type 2 diabetes: Role of exosomal SOD3.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- A nexus of lipid andFrontiers in endocrinology · 2022Review
- CaPflugers Archiv : European journal of physiology · 2022Review
- The dual role of the hexosamine biosynthetic pathway in cardiac physiology and pathophysiology.Frontiers in endocrinology · 2022Review
- Profile of crosstalk between glucose and lipid metabolic disturbance and diabetic cardiomyopathy: Inflammation and oxidative stress.Frontiers in endocrinology · 2022Review
- Cardiomyocyte protein O-GlcNAcylation is regulated by GFAT1 not GFAT2.Biochemical and biophysical research communications · 2021Article
- Glycation and Glycosylation in Cardiovascular Remodeling: Focus on Advanced Glycation End Products and O-Linked Glycosylations as Glucose-Related Pathogenetic Factors and Disease Markers.Journal of clinical medicine · 2021Review
7 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
We examined the role that enzymatic protein O-GlcNAcylation plays in the development of diabetic cardiomyopathy in a mouse model of Type 2 diabetes mellitus (DM2). Mice injected with low-dose streptozotocin and fed a high-fat diet developed mild hyperglycemia and obesity consistent with DM2. Studies were performed from 1 to 6 mo after initiating the DM2 protocol. After 1 mo, DM2 mice showed increased body weight, impaired fasting blood glucose, and hyperinsulinemia. Echocardiographic evaluation revealed left ventricular diastolic dysfunction by 2 mo and O-GlcNAcylation of several cardiac proteins and of nuclear transcription factor Sp1. By 4 mo, systolic dysfunction was observed and sarcoplasmic reticulum Ca(2+) ATPase expression decreased by 50%. Fibrosis was not observed at any timepoint in DM2 mice. Levels of the rate-limiting enzyme of the hexosamine biosynthetic pathway, glutamine:fructose-6-phosphate amidotransferase (GFAT) were increased as early as 2 mo. Fatty acids, which are elevated in DM2 mice, can possibly be linked to excessive protein O-GlcNAcylation levels, as cultured cardiac myocytes in normal glucose treated with oleic acid showed increased O-GlcNAcylation and GFAT levels. These data indicate that the early onset of diastolic dysfunction followed by the loss of systolic function, in the absence of cardiac hypertrophy or fibrosis, is associated with increased cardiac protein O-GlcNAcylation and increased O-GlcNAcylation levels of key calcium-handling proteins. A link between excessive protein O-GlcNAcylation and cardiac dysfunction is further supported by results showing that reducing O-GlcNAcylation by O-GlcNAcase overexpression improved cardiac function in the diabetic mouse. In addition, fatty acids play a role in stimulating excess O-GlcNAcylation. The nature and time course of changes observed in cardiac function suggest that protein O-GlcNAcylation plays a mechanistic role in the triggering of diabetic cardiomyopathy in DM2.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.