Gene expression in skeletal muscle biopsies from people with type 2 diabetes and relatives: differential regulation of insulin signaling pathways

J. Palsgaard; C. Brøns; M. Friedrichsen; H. Dominguez; M. Jensen; H. Storgaard; C. Spohr; C. Torp-Pedersen; R. Borup; P. De Meyts; A. Vaag; Jane Palsgaard Pedersen; Charlotte Brøns; Martin Friedrichsen; Helena Dominguez; Maja Lynderup Jensen; Heidi Storgaard; Camilla Spohr; Christian Torp-Pedersen; Rehannah Borup Helweg-Larsen; Pierre Marcel Joseph De Meyts; Allan Vaag

doi:10.1371/journal.pone.0006575

Gene expression in skeletal muscle biopsies from people with type 2 diabetes and relatives: differential regulation of insulin signaling pathways

J. Palsgaard, C. Brøns, M. Friedrichsen, H. Dominguez, M. Jensen, H. Storgaard, C. Spohr, C. Torp-Pedersen, R. Borup, P. De Meyts, A. Vaag, Jane Palsgaard Pedersen, Charlotte Brøns, Martin Friedrichsen, Helena Dominguez, Maja Lynderup Jensen, Heidi Storgaard, Camilla Spohr, Christian Torp-Pedersen, Rehannah Borup Helweg-LarsenPierre Marcel Joseph De Meyts, Allan Vaag

65 Citations (Scopus)

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. 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.

Original language	English
Journal	PLoS ONE
Volume	4
Issue number	8
Pages (from-to)	e6575
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0006575 https://doi.org/10.1371/journal.pone.0006575
Publication status	Published - 1 Jan 2009

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Palsgaard, J., Brøns, C., Friedrichsen, M., Dominguez, H., Jensen, M., Storgaard, H., Spohr, C., Torp-Pedersen, C., Borup, R., Meyts, P. D., Vaag, A., Pedersen, J. P., Brøns, C., Friedrichsen, M., Dominguez, H., Jensen, M. L., Storgaard, H., Spohr, C., Torp-Pedersen, C., ... Vaag, A. (2009). Gene expression in skeletal muscle biopsies from people with type 2 diabetes and relatives: differential regulation of insulin signaling pathways. PLoS ONE, 4(8), e6575. https://doi.org/10.1371/journal.pone.0006575, https://doi.org/10.1371/journal.pone.0006575

Palsgaard, J, Brøns, C, Friedrichsen, M, Dominguez, H, Jensen, M, Storgaard, H, Spohr, C, Torp-Pedersen, C, Borup, R, Meyts, PD, Vaag, A, Pedersen, JP, Brøns, C, Friedrichsen, M, Dominguez, H, Jensen, ML, Storgaard, H, Spohr, C, Torp-Pedersen, C, Helweg-Larsen, RB, De Meyts, PMJ & Vaag, A 2009, 'Gene expression in skeletal muscle biopsies from people with type 2 diabetes and relatives: differential regulation of insulin signaling pathways', PLoS ONE, vol. 4, no. 8, pp. e6575. https://doi.org/10.1371/journal.pone.0006575, https://doi.org/10.1371/journal.pone.0006575

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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. 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.",

author = "J. Palsgaard and C. Br{\o}ns and M. Friedrichsen and H. Dominguez and M. Jensen and H. Storgaard and C. Spohr and C. Torp-Pedersen and R. Borup and Meyts, {P. De} and A. Vaag and Pedersen, {Jane Palsgaard} and Charlotte Br{\o}ns and Martin Friedrichsen and Helena Dominguez and Jensen, {Maja Lynderup} and Heidi Storgaard and Camilla Spohr and Christian Torp-Pedersen and Helweg-Larsen, {Rehannah Borup} and {De Meyts}, {Pierre Marcel Joseph} and Allan Vaag",

note = "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",

year = "2009",

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T1 - Gene expression in skeletal muscle biopsies from people with type 2 diabetes and relatives: differential regulation of insulin signaling pathways

AU - Palsgaard, J.

AU - Brøns, C.

AU - Friedrichsen, M.

AU - Dominguez, H.

AU - Jensen, M.

AU - Storgaard, H.

AU - Spohr, C.

AU - Torp-Pedersen, C.

AU - Borup, R.

AU - Meyts, P. De

AU - Vaag, A.

AU - Pedersen, Jane Palsgaard

AU - Brøns, Charlotte

AU - Friedrichsen, Martin

AU - Dominguez, Helena

AU - Jensen, Maja Lynderup

AU - Storgaard, Heidi

AU - Spohr, Camilla

AU - Torp-Pedersen, Christian

AU - Helweg-Larsen, Rehannah Borup

AU - De Meyts, Pierre Marcel Joseph

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 - 2009/1/1

Y1 - 2009/1/1

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.

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 -

Gene expression in skeletal muscle biopsies from people with type 2 diabetes and relatives: differential regulation of insulin signaling pathways

Abstract

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