TY - JOUR
T1 - Gene expression in skeletal muscle biopsies from people with type 2 diabetes and relatives
T2 - differential regulation of insulin signaling pathways
AU - Palsgaard, Jane
AU - Brøns, Charlotte
AU - Friedrichsen, Martin
AU - Dominguez, Helena
AU - Jensen, Maja
AU - Storgaard, Heidi
AU - Spohr, Camilla
AU - Torp-Pedersen, Christian
AU - Borup, Rehannah
AU - De Meyts, Pierre
AU - Vaag, Allan
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Adult
KW - Biopsy
KW - Blotting, Western
KW - Case-Control Studies
KW - Diabetes Mellitus, Type 2
KW - Gene Expression Profiling
KW - Humans
KW - Insulin
KW - Male
KW - Muscle, Skeletal
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Signal Transduction
U2 - 10.1371/journal.pone.0006575
DO - 10.1371/journal.pone.0006575
M3 - Journal article
C2 - 19668377
SN - 1932-6203
VL - 4
SP - e6575
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 8
ER -
