A gene expression signature for insulin resistance

Article

Konstantopoulos, Nicky, Foletta, Victoria C., Segal, David H., Shields, Katherine A., Sanigorski, Andrew, Windmill, Kelly, Swinton, Courtney, Connor, Tim, Wanyonyi, Stephen, Dyer, Thomas D., Fahey, Richard P., Watt, Rose A., Curran, Joanne E., Molero, Juan C., Krippner, Guy, Collier, Greg R., James, David E., Blangero, John, Jowett, Jeremy B. and Walder, Ken R.. 2011. "A gene expression signature for insulin resistance." Physiological Genomics. 43 (3), pp. 110-120. https://doi.org/10.1152/physiolgenomics.00115.2010
Article Title

A gene expression signature for insulin resistance

ERA Journal ID14629
Article CategoryArticle
AuthorsKonstantopoulos, Nicky (Author), Foletta, Victoria C. (Author), Segal, David H. (Author), Shields, Katherine A. (Author), Sanigorski, Andrew (Author), Windmill, Kelly (Author), Swinton, Courtney (Author), Connor, Tim (Author), Wanyonyi, Stephen (Author), Dyer, Thomas D. (Author), Fahey, Richard P. (Author), Watt, Rose A. (Author), Curran, Joanne E. (Author), Molero, Juan C. (Author), Krippner, Guy (Author), Collier, Greg R. (Author), James, David E. (Author), Blangero, John (Author), Jowett, Jeremy B. (Author) and Walder, Ken R. (Author)
Journal TitlePhysiological Genomics
Journal Citation43 (3), pp. 110-120
Number of Pages11
Year2011
PublisherAmerican Physiological Society
Place of PublicationUnited States
ISSN1094-8341
1531-2267
Digital Object Identifier (DOI)https://doi.org/10.1152/physiolgenomics.00115.2010
Web Address (URL)https://journals.physiology.org/doi/full/10.1152/physiolgenomics.00115.2010
Abstract

Insulin resistance is a heterogeneous disorder caused by a range of genetic and environmental factors, and we hypothesize that its etiology varies considerably between individuals. This heterogeneity provides significant challenges to the development of effective therapeutic regimes for long-term management of type 2 diabetes. We describe a novel strategy, using large-scale gene expression profiling, to develop a gene expression signature (GES) that reflects the overall state of insulin resistance in cells and patients. The GES was developed from 3T3-L1 adipocytes that were made “insulin resistant” by treatment with tumor necrosis factor-α (TNF-α) and then reversed with aspirin and troglitazone (“resensitized”). The GES consisted of five genes whose expression levels best discriminated between the insulin-resistant and insulin-resensitized states. We then used this GES to screen a compound library for agents that affected the GES genes in 3T3-L1 adipocytes in a way that most closely resembled the changes seen when insulin resistance was successfully reversed with aspirin and troglitazone. This screen identified both known and new insulin-sensitizing compounds including nonsteroidal anti-inflammatory agents, β-adrenergic antagonists, β-lactams, and sodium channel blockers. We tested the biological relevance of this GES in participants in the San Antonio Family Heart Study (n = 1,240) and showed that patients with the lowest GES scores were more insulin resistant (according to HOMA_IR and fasting plasma insulin levels; P < 0.001). These findings show that GES technology can be used for both the discovery of insulin-sensitizing compounds and the characterization of patients into subtypes of insulin resistance according to GES scores, opening the possibility of developing a personalized medicine approach to type 2 diabetes.

Keywordsmicroarray; screening; diabetes;personalized medicine; tumor-necrosis-factor;
Contains Sensitive ContentDoes not contain sensitive content
ANZSRC Field of Research 2020320208. Endocrinology
320213. Medical genetics (excl. cancer genetics)
Public Notes

Files associated with this item cannot be displayed due to copyright restrictions.

Institution of OriginUniversity of Southern Queensland
Byline AffiliationsDeakin University
Baker Heart and Diabetes Institute, Australia
Texas Biomedical Research Institute, United States
Verva Pharmaceuticals, Australia
ChemGenex Pharmaceuticals, Australia
Garvan Institute of Medical Research, Australia
Permalink -

https://research.usq.edu.au/item/q3x20/a-gene-expression-signature-for-insulin-resistance

Log in to edit
  • 1394
    total views
  • 10
    total downloads
  • 1
    views this month
  • 0
    downloads this month

Export as

Related outputs

Functional Foods Research Group: Stephen Wanyonyi
Wanyonyi, Stephen. Functional Foods Research Group: Stephen Wanyonyi. Toowoomba. https://doi.org/10.26192/2z6r-wx03
Saskatoon Berry Amelanchier alnifolia Regulates Glucose Metabolism and Improves Cardiovascular and Liver Signs of Diet-Induced Metabolic Syndrome in Rats
du Preez, Ryan, Wanyonyi, Stephen, Mouatt, Peter, Panchal, Sunil K. and Brown, Lindsay. 2020. "Saskatoon Berry Amelanchier alnifolia Regulates Glucose Metabolism and Improves Cardiovascular and Liver Signs of Diet-Induced Metabolic Syndrome in Rats." Nutrients. 12 (4), pp. 1-16. https://doi.org/10.3390/nu12040931
Linseed components are more effective than whole linseed in reversing diet-induced metabolic syndrome in rats
Shafie, Siti Raihanah, Wanyonyi, Stephen, Panchal, Sunil K. and Brown, Lindsay. 2019. "Linseed components are more effective than whole linseed in reversing diet-induced metabolic syndrome in rats." Nutrients. 11 (1677), pp. 1-16. https://doi.org/10.3390/nu11071677
Achacha (Garcinia humilis) Rind Improves Cardiovascular Function in Rats with Diet-Induced Metabolic Syndrome
John, Oliver D., Wanyonyi, Stephen, Mouatt, Peter, Panchal, Sunil K. and Brown, Lindsay. 2018. "Achacha (Garcinia humilis) Rind Improves Cardiovascular Function in Rats with Diet-Induced Metabolic Syndrome." Nutrients. 10 (10), pp. 1-15. https://doi.org/10.3390/nu10101425
Kappaphycus alvarezii as a food supplement prevents diet-induced metabolic syndrome in rats
Wanyonyi, Stephen, du Preez, Ryan, Brown, Lindsay, Paul, Nicholas A. and Panchal, Sunil K.. 2017. "Kappaphycus alvarezii as a food supplement prevents diet-induced metabolic syndrome in rats." Nutrients. 9 (11). https://doi.org/10.3390/nu9111261
The comparative genomics of monotremes, marsupials, and pinnipeds: models to examine the functions of milk proteins
Sharp, Julie A., Watt, Ashalyn, Bisana, Swathi, Modepalli, Vengama, Wanyonyi, Stephen, Kumar, Amit, Kwek, Joly, Collins, Rod, Lefevre, Christopher and Nicholas, Kevin R.. 2014. "The comparative genomics of monotremes, marsupials, and pinnipeds: models to examine the functions of milk proteins ." Singh, Harjinder, Boland, Mike and Thompson, Abby (ed.) Milk proteins: from expression to food. Amsterdam, The Netherlands. Elsevier. pp. 75-112
Inhibition of inosine monophosphate dehydrogenase reduces adipogenesis and diet-induced obesity
Su, Hua, Gunter, Jennifer H., de Vries, Melissa, Connor, Tim, Wanyonyi, Stephen, Newell, Felicity S., Segal, David, Molero, Juan Carlos, Reizes, Ofer, Prins, Johannes B., Hutley, Louise J., Walder, Ken and Whitehead, Jonathan P.. 2009. "Inhibition of inosine monophosphate dehydrogenase reduces adipogenesis and diet-induced obesity." Biochemical and Biophysical Research Communications. 386 (2), pp. 351-355. https://doi.org/10.1016/j.bbrc.2009.06.040
Selenium, vanadium, and chromium as micronutrients to improve metabolic syndrome
Panchal, Sunil K., Wanyonyi, Stephen and Brown, Lindsay. 2017. "Selenium, vanadium, and chromium as micronutrients to improve metabolic syndrome." Current Hypertension Reports. 19 (3), pp. 10-20. https://doi.org/10.1007/s11906-017-0701-x
Tammar wallaby mammary cathelicidins are differentially expressed during lactation and exhibit antimicrobial and cell proliferative activity
Wanyonyi, Stephen S., Sharp, Julie A., Khalil, Elie, Lefevre, Christophe and Nicholas, Kevin R.. 2011. "Tammar wallaby mammary cathelicidins are differentially expressed during lactation and exhibit antimicrobial and cell proliferative activity." Comparative Biochemistry and Physiology Part A: Molecular and Integrative Physiology. 160 (3), pp. 431-439. https://doi.org/10.1016/j.cbpa.2011.07.015
Methazolamide is a new hepatic insulin sensitizer that lowers blood glucose in vivo
Konstantopoulos, Nicky, Molero, Juan C., McGee, Sean L., Spolding, Briana, Connor, Tim, de Vries, Melissa, Wanyonyi, Stephen, Fahey, Richard, Morrison, Shona, Swinton, Courtney, Jones, Sharon, Cooper, Adrian, Garcia-Guerra, Lucia, Foletta, Victoria C., Krippner, Guy, Andrikopoulos, Sofianos and Walder, Ken R.. 2012. "Methazolamide is a new hepatic insulin sensitizer that lowers blood glucose in vivo." Diabetes. 61 (8), pp. 2146-2154. https://doi.org/10.2337/db11-0578
The tammar wallaby: a model system to examine domain-specific delivery of milk protein bioactives
Nicholas, Kevin, Sharp, Julie, Watt, Ashalyn, Wanyonyi, Stephen, Crowley, Tamsyn, Gillespie, Meagan and Lefevre, Christophe. 2012. "The tammar wallaby: a model system to examine domain-specific delivery of milk protein bioactives." Seminars in Cell and Developmental Biology. 23 (5), pp. 547-556. https://doi.org/10.1016/j.semcdb.2012.03.016
The extracellular matrix regulates MaeuCath1a gene expression
Wanyonyi, Stephen S., Lefevre, Christophe, Sharp, Julie A. and Nicholas, Kevin R.. 2013. "The extracellular matrix regulates MaeuCath1a gene expression." Developmental and Comparative Immunology. 40 (3-4), pp. 289-299. https://doi.org/10.1016/j.dci.2013.02.010
The extracellular matrix locally regulates asynchronous concurrent lactation in tammar wallaby (Macropus eugenii)
Wanyonyi, Stephen S., Lefevre, Christophe, Sharp, Julie A. and Nicholas, Kevin R.. 2013. "The extracellular matrix locally regulates asynchronous concurrent lactation in tammar wallaby (Macropus eugenii)." Matrix Biology. 32 (6), pp. 342-351. https://doi.org/10.1016/j.matbio.2013.02.001
The tammar wallaby: a marsupial model to examine the timed delivery and role of bioactives in milk
Sharp, Julie A., Wanyonyi, Stephen, Modepalli, Vengama, Watt, Ashalyn, Kuruppath, Sanjana, Hinds, Lyn A., Kumar, Amit, Abud, Helen E., Lefevre, Christophe and Nicholas, Kevin R.. 2017. "The tammar wallaby: a marsupial model to examine the timed delivery and role of bioactives in milk." General and Comparative Endocrinology. 244, pp. 164-177. https://doi.org/10.1016/j.ygcen.2016.08.007
Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci
Kooner, Jaspal S., Saleheem, Danish, Sim, Xueling, Sehmi, Joban, Zhang, Weihua, Frossard, Philippe, Been, Latonya F., Chia, Kee-Seng, Dimas, Antigone S., Hassanali, Neelam, Jafar, Tazeen, Jowett, Jeremy B. M., Li, Xinzhong, Radha, Venkatesan, Rees, Simon D., Takeuchi, Fumihiko, Young, Robin and Pinidiyapathirage, Janani M.. 2011. "Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci." Nature Genetics. 43 (10), pp. 984-989. https://doi.org/10.1038/ng.921
Transcriptome analysis of mammary epithelial cell gene expression reveals novel roles of the extracellular matrix
Wanyonyi, Stephen S., Kumar, Amit, Du Preez, Ryan, Lefevre, Christophe and Nicholas, Kevin R.. 2017. "Transcriptome analysis of mammary epithelial cell gene expression reveals novel roles of the extracellular matrix." Biochemistry and Biophysics Reports. 12, pp. 120-128. https://doi.org/10.1016/j.bbrep.2017.08.013
Activation of the selenoprotein SEPS1 gene expression by pro-inflammatory cytokines in HepG2 cells
Gao, Yuan, Hannan, Nicholas R. F., Wanyonyi, Stephen, Konstantopolous, Nicky, Pagnon, Joanne, Feng, Helen C., Jowett, Jeremy B. M., Kim, Kee-Hong, Walder, Ken and Collier, Greg R.. 2006. "Activation of the selenoprotein SEPS1 gene expression by pro-inflammatory cytokines in HepG2 cells." Cytokine. 33 (5), pp. 246-251. https://doi.org/10.1016/j.cyto.2006.02.005