Gene expression profiling in the type 1 diabetes rat diaphragm.
BACKGROUND:Respiratory muscle contractile performance is impaired by diabetes, mechanisms of which included altered carbohydrate and lipid metabolism, oxidative stress and changes in membrane electrophysiology. The present study examined to what extent these cellular perturbations involve changes in...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-11-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2773011?pdf=render |
| _version_ | 1818850987051319296 |
|---|---|
| author | Erik van Lunteren Michelle Moyer |
| author_facet | Erik van Lunteren Michelle Moyer |
| author_sort | Erik van Lunteren |
| collection | DOAJ |
| description | BACKGROUND:Respiratory muscle contractile performance is impaired by diabetes, mechanisms of which included altered carbohydrate and lipid metabolism, oxidative stress and changes in membrane electrophysiology. The present study examined to what extent these cellular perturbations involve changes in gene expression. METHODOLOGY/PRINCIPAL FINDINGS:Diaphragm muscle from streptozotocin-diabetic rats was analyzed with Affymetrix gene expression arrays. Diaphragm from diabetic rats had 105 genes with at least +/-2-fold significantly changed expression (55 increased, 50 decreased), and these were assigned to gene ontology groups based on over-representation analysis using DAVID software. There was increased expression of genes involved in palmitoyl-CoA hydrolase activity (a component of lipid metabolism) (P = 0.037, n = 2 genes, fold change 4.2 to 27.5) and reduced expression of genes related to carbohydrate metabolism (P = 0.000061, n = 8 genes, fold change -2.0 to -8.5). Other gene ontology groups among upregulated genes were protein ubiquitination (P = 0.0053, n = 4, fold change 2.2 to 3.4), oxidoreductase activity (P = 0.024, n = 8, fold change 2.1 to 6.0), and morphogenesis (P = 0.012, n = 10, fold change 2.1 to 4.3). Other downregulated gene groups were extracellular region (including extracellular matrix and collagen) (P = 0.00032, n = 13, fold change -2.2 to -3.7) and organogenesis (P = 0.032, n = 7, fold change -2.1 to -3.7). Real-time PCR confirmed the directionality of changes in gene expression for 30 of 31 genes tested. CONCLUSIONS/SIGNIFICANCE:These data indicate that in diaphragm muscle type 1 diabetes increases expression of genes involved in lipid energetics, oxidative stress and protein ubiquitination, decreases expression of genes involved in carbohydrate metabolism, and has little effect on expression of ion channel genes. Reciprocal changes in expression of genes involved in carbohydrate and lipid metabolism may change the availability of energetic substrates and thereby directly modulate fatigue resistance, an important issue for a muscle like the diaphragm which needs to contract without rest for the entire lifetime of the organism. |
| first_indexed | 2024-12-19T06:57:51Z |
| format | Article |
| id | doaj.art-a56fb64d6ece498e9bead809fae2e81f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T06:57:51Z |
| publishDate | 2009-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-a56fb64d6ece498e9bead809fae2e81f2022-12-21T20:31:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-11-01411e783210.1371/journal.pone.0007832Gene expression profiling in the type 1 diabetes rat diaphragm.Erik van LunterenMichelle MoyerBACKGROUND:Respiratory muscle contractile performance is impaired by diabetes, mechanisms of which included altered carbohydrate and lipid metabolism, oxidative stress and changes in membrane electrophysiology. The present study examined to what extent these cellular perturbations involve changes in gene expression. METHODOLOGY/PRINCIPAL FINDINGS:Diaphragm muscle from streptozotocin-diabetic rats was analyzed with Affymetrix gene expression arrays. Diaphragm from diabetic rats had 105 genes with at least +/-2-fold significantly changed expression (55 increased, 50 decreased), and these were assigned to gene ontology groups based on over-representation analysis using DAVID software. There was increased expression of genes involved in palmitoyl-CoA hydrolase activity (a component of lipid metabolism) (P = 0.037, n = 2 genes, fold change 4.2 to 27.5) and reduced expression of genes related to carbohydrate metabolism (P = 0.000061, n = 8 genes, fold change -2.0 to -8.5). Other gene ontology groups among upregulated genes were protein ubiquitination (P = 0.0053, n = 4, fold change 2.2 to 3.4), oxidoreductase activity (P = 0.024, n = 8, fold change 2.1 to 6.0), and morphogenesis (P = 0.012, n = 10, fold change 2.1 to 4.3). Other downregulated gene groups were extracellular region (including extracellular matrix and collagen) (P = 0.00032, n = 13, fold change -2.2 to -3.7) and organogenesis (P = 0.032, n = 7, fold change -2.1 to -3.7). Real-time PCR confirmed the directionality of changes in gene expression for 30 of 31 genes tested. CONCLUSIONS/SIGNIFICANCE:These data indicate that in diaphragm muscle type 1 diabetes increases expression of genes involved in lipid energetics, oxidative stress and protein ubiquitination, decreases expression of genes involved in carbohydrate metabolism, and has little effect on expression of ion channel genes. Reciprocal changes in expression of genes involved in carbohydrate and lipid metabolism may change the availability of energetic substrates and thereby directly modulate fatigue resistance, an important issue for a muscle like the diaphragm which needs to contract without rest for the entire lifetime of the organism.http://europepmc.org/articles/PMC2773011?pdf=render |
| spellingShingle | Erik van Lunteren Michelle Moyer Gene expression profiling in the type 1 diabetes rat diaphragm. PLoS ONE |
| title | Gene expression profiling in the type 1 diabetes rat diaphragm. |
| title_full | Gene expression profiling in the type 1 diabetes rat diaphragm. |
| title_fullStr | Gene expression profiling in the type 1 diabetes rat diaphragm. |
| title_full_unstemmed | Gene expression profiling in the type 1 diabetes rat diaphragm. |
| title_short | Gene expression profiling in the type 1 diabetes rat diaphragm. |
| title_sort | gene expression profiling in the type 1 diabetes rat diaphragm |
| url | http://europepmc.org/articles/PMC2773011?pdf=render |
| work_keys_str_mv | AT erikvanlunteren geneexpressionprofilinginthetype1diabetesratdiaphragm AT michellemoyer geneexpressionprofilinginthetype1diabetesratdiaphragm |