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

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Prior, Matthew, Foletta, Victoria C, Jowett, Jeremy, Segal, David, Carless, Melanie, Curran, Joanne, Dyer, Tom, Moses, Eric, McAinch, Andrew, Konstantopoulos, Nicky, Bozaoglu, Kiymet, Collier, Greg R, Cameron-Smith, David, 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

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.

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Item type Article
URI https://vuir.vu.edu.au/id/eprint/4536
DOI https://doi.org/10.1016/j.metabol.2009.11.002
Official URL http://www.sciencedirect.com/science/article/pii/S...
Subjects Historical > Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
Historical > FOR Classification > 1116 Medical Physiology
Historical > SEO Classification > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
Keywords ResPubID17477, ResPubID19640, ResPubID20019, skeletal muscle, metabolic syndrome, diabetes
Citations in Scopus 9 - View on Scopus
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