title: Gene expression in skeletal muscle biopsies from people with type 2 diabetes and relatives: differential regulation of insulin signaling pathways.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors: Receptor Systems Biology Laboratory, Hagedorn Research Institute, Novo Nordisk, Gentofte, Denmark. JPAG@novonordisk.com
authors: Jane
authors: J
authors: Palsgaard
authors: Charlotte
authors: C
authors: Brøns
authors: Martin
authors: M
authors: Friedrichsen
authors: Helena
authors: H
authors: Dominguez
authors: Maja
authors: M
authors: Jensen
authors: Heidi
authors: H
authors: Storgaard
authors: Camilla
authors: C
authors: Spohr
authors: Christian
authors: C
authors: Torp-Pedersen
authors: Rehannah
authors: R
authors: Borup
authors: Pierre
authors: P
authors: De Meyts
authors: Allan
authors: A
authors: Vaag
mesh_terms: D000328:Adult; D001706:Biopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D007328:Insulin