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Gene expression profiling in the type 1 diabetes rat diaphragm
Erik van Lunteren1, Michelle Moyer
1Pulmonary, Critical Care and Sleep Division, Department of Medicine, Louis Stokes Cleveland Department of Veterans Affairs Medical Center and Case Western Reserve University, Cleveland, OH, USA. exv4@cwru.edu
Plos One
|November 17, 2009
Summary
Diabetes impairs diaphragm muscle by altering gene expression. Key changes include increased lipid metabolism and oxidative stress genes, and decreased carbohydrate metabolism genes, impacting muscle function.
Area of Science:
- Molecular Biology
- Physiology
- Metabolic Disorders
Background:
- Diabetes mellitus is known to impair respiratory muscle contractile performance.
- Underlying mechanisms involve altered metabolism, oxidative stress, and membrane electrophysiology.
- The role of gene expression changes in these perturbations remains to be fully elucidated.
Purpose of the Study:
- To investigate the extent to which cellular perturbations in diabetic respiratory muscle are associated with changes in gene expression.
- To identify specific genes and pathways affected by diabetes in diaphragm muscle.
Main Methods:
- Gene expression profiling of diaphragm muscle from streptozotocin-induced diabetic rats using Affymetrix arrays.
- Over-representation analysis using DAVID software to assign differentially expressed genes to gene ontology groups.
- Validation of gene expression changes using real-time polymerase chain reaction (PCR).
Main Results:
- Diaphragm muscle from diabetic rats exhibited 105 genes with significantly altered expression (≥2-fold change).
- Upregulated genes were associated with lipid metabolism (palmitoyl-CoA hydrolase activity), protein ubiquitination, oxidoreductase activity, and morphogenesis.
- Downregulated genes were linked to carbohydrate metabolism, extracellular region (including extracellular matrix), and organogenesis.
Conclusions:
- Type 1 diabetes alters gene expression in diaphragm muscle, favoring lipid energetics and oxidative stress pathways while downregulating carbohydrate metabolism.
- Reciprocal changes in carbohydrate and lipid metabolism gene expression may alter substrate availability, potentially modulating diaphragm fatigue resistance.
- Diabetes has minimal impact on ion channel gene expression in the diaphragm.
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