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

N1 - Keywords: Adult; Biopsy; Blotting, Western; Case-Control Studies; Diabetes Mellitus, Type 2; Gene Expression Profiling; Humans; Insulin; Male; Muscle, Skeletal; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction

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

VL - 4

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 8

M1 - e6575

ER -