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

Matthew J. Prior, Victoria C. Foletta, Jeremy B. Jowett, David H. Segal, Melanie A. Carless, Joanne E. Curran, Tom D. Dyer, Eric K. Moses, Andrew J. McAinch, Nicky Konstantopoulos, Kiymet Bozaoglu, Greg R. Collier, David Cameron-Smith, John Blangero, Ken R. Walder

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1057-1064
Number of pages8
JournalMetabolism: Clinical and Experimental
Volume59
Issue number7
DOIs
StatePublished - Jul 2010
Externally publishedYes

Fingerprint

Type 2 Diabetes Mellitus
Skeletal Muscle
Glucose
Rodentia
Phenotype
Messenger RNA
Skeletal Muscle Fibers
Gonads
RNA Interference
Nervous System Diseases
Genes
Single Nucleotide Polymorphism
Blood Glucose
Fasting
Homeostasis
Animal Models
Obesity
Maintenance
Insulin
Gene Expression

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Prior, M. J., Foletta, V. C., Jowett, J. B., Segal, D. H., Carless, M. A., Curran, J. E., ... Walder, K. R. (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. https://doi.org/10.1016/j.metabol.2009.11.002

The characterization of Abelson helper integration site-1 in skeletal muscle and its links to the metabolic syndrome. / Prior, Matthew J.; Foletta, Victoria C.; Jowett, Jeremy B.; Segal, David H.; Carless, Melanie A.; Curran, Joanne E.; Dyer, Tom D.; Moses, Eric K.; McAinch, Andrew J.; Konstantopoulos, Nicky; Bozaoglu, Kiymet; Collier, Greg R.; Cameron-Smith, David; Blangero, John; Walder, Ken R.

In: Metabolism: Clinical and Experimental, Vol. 59, No. 7, 07.2010, p. 1057-1064.

Research output: Contribution to journalArticle

Prior, MJ, Foletta, VC, Jowett, JB, Segal, DH, Carless, MA, Curran, JE, Dyer, TD, Moses, EK, McAinch, AJ, Konstantopoulos, N, Bozaoglu, K, Collier, GR, Cameron-Smith, D, Blangero, J & Walder, KR 2010, 'The characterization of Abelson helper integration site-1 in skeletal muscle and its links to the metabolic syndrome', Metabolism: Clinical and Experimental, vol. 59, no. 7, pp. 1057-1064. https://doi.org/10.1016/j.metabol.2009.11.002
Prior, Matthew J. ; Foletta, Victoria C. ; Jowett, Jeremy B. ; Segal, David H. ; Carless, Melanie A. ; Curran, Joanne E. ; Dyer, Tom D. ; Moses, Eric K. ; McAinch, Andrew J. ; Konstantopoulos, Nicky ; Bozaoglu, Kiymet ; Collier, Greg R. ; Cameron-Smith, David ; Blangero, John ; Walder, Ken R. / The characterization of Abelson helper integration site-1 in skeletal muscle and its links to the metabolic syndrome. In: Metabolism: Clinical and Experimental. 2010 ; Vol. 59, No. 7. pp. 1057-1064.
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