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The characterization of Abelson helper integration site–1 in skeletal muscle and its links to the metabolic syndrome

Prior, Matthew and Foletta, Victoria C and Jowett, Jeremy and Segal, David and Carless, Melanie and Curran, Joanne and Dyer, Tom and Moses, Eric and McAinch, Andrew and Konstantopoulos, Nicky and Bozaoglu, Kiymet and Collier, Greg R and Cameron-Smith, David and Blangero, John and Walder, Ken (2010) The characterization of Abelson helper integration site–1 in skeletal muscle and its links to the metabolic syndrome. Metabolism Clinical and Experimental, 59 (7). 1057-1064 . ISSN 0026-0495

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Abstract

The human Abelson helper integration site–1 (AHI1) gene is associated with both neurologic and hematologic disorders; however, it is also located in a chromosomal region linked to metabolic syndrome phenotypes and was identified as a type 2 diabetes mellitus susceptibility gene from a genomewide association study. To further define a possible role in type 2 diabetes mellitus development, AHI1 messenger RNA expression levels were investigated in a range of tissues and found to be highly expressed in skeletal muscle as well as displaying elevated levels in brain regions and gonad tissues. Further analysis in a rodent polygenic animal model of obesity and type 2 diabetes mellitus identified increased Ahi-1 messenger RNA levels in red gastrocnemius muscle from fasted impaired glucose–tolerant and diabetic rodents compared with healthy animals (P < .002). Moreover, elevated gene expression levels were confirmed in skeletal muscle from fasted obese and type 2 diabetes mellitus human subjects (P < .02). RNAi-mediated suppression of Ahi-1 resulted in increased glucose transport in rat L6 myotubes in both the basal and insulin-stimulated states (P < .01). Finally, single nucleotide polymorphism association studies identified 2 novel AHI1 genetic variants linked with fasting blood glucose levels in Mexican American subjects (P < .037). These findings indicate a novel role for AHI1 in skeletal muscle and identify additional genetic links with metabolic syndrome phenotypes suggesting an involvement of AHI1 in the maintenance of glucose homeostasis and type 2 diabetes mellitus progression.

Item Type: Article
Uncontrolled Keywords: ResPubID17477, ResPubID19640, ResPubID20019, skeletal muscle, metabolic syndrome, diabetes
Subjects: Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
FOR Classification > 1116 Medical Physiology
SEO Classification > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
Depositing User: VUIR
Date Deposited: 14 Feb 2012 01:20
Last Modified: 05 Feb 2015 01:04
URI: http://vuir.vu.edu.au/id/eprint/4536
DOI: 10.1016/j.metabol.2009.11.002
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Citations in Scopus: 4 - View on Scopus

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