Gene expression in skeletal muscle biopsies from people with type 2 diabetes and relatives: differential regulation of insulin signaling pathways
| Autor: | Charlotte Brøns, Martin Friedrichsen, Pierre De Meyts, Helena Dominguez, Heidi Storgaard, Jane Palsgaard, Allan Vaag, Camilla Spohr, Rehannah Borup, Christian Torp-Pedersen, Maja Jensen |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_specialty medicine.medical_treatment Biopsy Blotting Western lcsh:Medicine Disease Type 2 diabetes Cell Biology/Cell Signaling Internal medicine medicine Humans Insulin First-degree relatives Muscle Skeletal lcsh:Science Cell Biology/Gene Expression Genetics and Genomics/Genetics of Disease Regulation of gene expression Multidisciplinary biology Physiology/Endocrinology Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling lcsh:R Case-control study medicine.disease Insulin receptor Endocrinology Diabetes Mellitus Type 2 Case-Control Studies biology.protein lcsh:Q Epigenetics of diabetes Type 2 Research Article Signal Transduction |
| Zdroj: | PLoS ONE, Vol 4, Iss 8, p e6575 (2009) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Background Gene expression alterations have previously been associated with type 2 diabetes, however whether these changes are primary causes or secondary effects of type 2 diabetes is not known. As healthy first degree relatives of people with type 2 diabetes have an increased risk of developing type 2 diabetes, they provide a good model in the search for primary causes of the disease. Methods/Principal Findings We determined gene expression profiles in skeletal muscle biopsies from Caucasian males with type 2 diabetes, healthy first degree relatives, and healthy controls. Gene expression was measured using Affymetrix Human Genome U133 Plus 2.0 Arrays covering the entire human genome. These arrays have not previously been used for this type of study. We show for the first time that genes involved in insulin signaling are significantly upregulated in first degree relatives and significantly downregulated in people with type 2 diabetes. On the individual gene level, 11 genes showed altered expression levels in first degree relatives compared to controls, among others KIF1B and GDF8 (myostatin). LDHB was found to have a decreased expression in both groups compared to controls. Conclusions/Significance We hypothesize that increased expression of insulin signaling molecules in first degree relatives of people with type 2 diabetes, work in concert with increased levels of insulin as a compensatory mechanism, counter-acting otherwise reduced insulin signaling activity, protecting these individuals from severe insulin resistance. This compensation is lost in people with type 2 diabetes where expression of insulin signaling molecules is reduced. |
| Databáze: | OpenAIRE |
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