The characterization of Abelson helper integration site-1 in skeletal muscle and its links to the metabolic syndrome
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 ass...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal Article |
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W.B. Saunders Co.
2010
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| Online Access: | http://hdl.handle.net/20.500.11937/36588 |
| _version_ | 1848754812261236736 |
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| author | Prior, M. Foletta, V. Jowett, J. Segal, D. Carless, M. Curran, J. Dyer, T. Moses, Eric McAinch, A. Konstantopoulos, N. Bozaoglu, K. Collier, G. Cameron-Smith, D. Blangero, J. Walder, K. |
| author_facet | Prior, M. Foletta, V. Jowett, J. Segal, D. Carless, M. Curran, J. Dyer, T. Moses, Eric McAinch, A. Konstantopoulos, N. Bozaoglu, K. Collier, G. Cameron-Smith, D. Blangero, J. Walder, K. |
| author_sort | Prior, M. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. © 2010 Elsevier Inc. All rights reserved. |
| first_indexed | 2025-11-14T08:46:21Z |
| format | Journal Article |
| id | curtin-20.500.11937-36588 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:46:21Z |
| publishDate | 2010 |
| publisher | W.B. Saunders Co. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-365882018-03-29T09:08:49Z The characterization of Abelson helper integration site-1 in skeletal muscle and its links to the metabolic syndrome Prior, M. Foletta, V. Jowett, J. Segal, D. Carless, M. Curran, J. Dyer, T. Moses, Eric McAinch, A. Konstantopoulos, N. Bozaoglu, K. Collier, G. Cameron-Smith, D. Blangero, J. Walder, K. 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. © 2010 Elsevier Inc. All rights reserved. 2010 Journal Article http://hdl.handle.net/20.500.11937/36588 10.1016/j.metabol.2009.11.002 W.B. Saunders Co. restricted |
| spellingShingle | Prior, M. Foletta, V. Jowett, J. Segal, D. Carless, M. Curran, J. Dyer, T. Moses, Eric McAinch, A. Konstantopoulos, N. Bozaoglu, K. Collier, G. Cameron-Smith, D. Blangero, J. Walder, K. The characterization of Abelson helper integration site-1 in skeletal muscle and its links to the metabolic syndrome |
| title | The characterization of Abelson helper integration site-1 in skeletal muscle and its links to the metabolic syndrome |
| title_full | The characterization of Abelson helper integration site-1 in skeletal muscle and its links to the metabolic syndrome |
| title_fullStr | The characterization of Abelson helper integration site-1 in skeletal muscle and its links to the metabolic syndrome |
| title_full_unstemmed | The characterization of Abelson helper integration site-1 in skeletal muscle and its links to the metabolic syndrome |
| title_short | The characterization of Abelson helper integration site-1 in skeletal muscle and its links to the metabolic syndrome |
| title_sort | characterization of abelson helper integration site-1 in skeletal muscle and its links to the metabolic syndrome |
| url | http://hdl.handle.net/20.500.11937/36588 |