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- Title
Maladaptive response following glucose overload in GLUT4‐overexpressing H9C2 cardiomyoblasts.
- Authors
Stratmann, Bernd; Eggers, Britta; Mattern, Yvonne; de Carvalho, Tayana Silva; Marcus‐Alic, Katrin; Tschoepe, Diethelm
- Abstract
Background: Glucose overload drives diabetic cardiomyopathy by affecting the tricarboxylic acid pathway. However, it is still unknown how cells could overcome massive chronic glucose influx on cellular and structural level. Methods/Materials: Expression profiles of hyperglycemic, glucose transporter‐4 (GLUT4) overexpressing H9C2 (KE2) cardiomyoblasts loaded with 30 mM glucose (KE230L) and wild type (WT) cardiomyoblasts loaded with 30 mM glucose (WT30L) were compared using proteomics, real‐time polymerase quantitative chain reaction analysis, or Western blotting, and immunocytochemistry. Results: The findings suggest that hyperglycemic insulin‐sensitive cells at the onset of diabetic cardiomyopathy present complex changes in levels of structural cell‐related proteins like tissue inhibitor of metalloproteases‐1 (1.3 fold), intercellular adhesion molecule 1 (1.8 fold), type‐IV‐collagen (3.2 fold), chaperones (Glucose‐Regulated Protein 78: 1.8 fold), autophagy (Autophagosome Proteins LC3A, LC3B: 1.3 fold), and in unfolded protein response (UPR; activating transcription factor 6α expression: 2.3 fold and processing: 2.4 fold). Increased f‐actin levels were detectable with glucose overload by immnocytochemistry. Effects on energy balance (1.6 fold), sirtuin expression profile (Sirtuin 1: 0.7 fold, sirtuin 3: 1.9 fold, and sirtuin 6: 4.2 fold), and antioxidant enzymes (Catalase: 0.8 fold and Superoxide dismutase 2: 1.5 fold) were detected. Conclusion: In conclusion, these findings implicate induction of chronic cell distress by sustained glucose accumulation with a non‐compensatory repair reaction not preventing final cell death. This might explain the chronic long lasting pathogenesis observed in developing heart failure in diabetes mellitus.
- Subjects
GLUCOSE-regulated proteins; INSULIN; CD54 antigen; UNFOLDED protein response; GLUCOSE; CYTOSKELETAL proteins; DIABETIC cardiomyopathy
- Publication
Diabetes, Obesity & Metabolism, 2024, Vol 26, Issue 6, p2379
- ISSN
1462-8902
- Publication type
Article
- DOI
10.1111/dom.15553