| Androgen receptor CAG repeat length polymorphism modifies the impact of testosterone on insulin sensitivity in men. | |
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MedLine Citation:
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PMID: 21444647 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Low circulating testosterone concentrations have been associated with insulin resistance (IR). Androgen action is mediated by the androgen receptor (AR) whose activity is modulated by a polymorphic CAG repeat sequence within exon 1. An interaction between testosterone and CAG repeat length (CAG length) with respect to IR has been described in women. OBJECTIVE: We investigated such a putative interaction between testosterone and the CAG length with respect to IR in men with normal glucose tolerance. DESIGN: Cross-sectional study. METHODS: In 113 non-diabetic men calculated free testosterone, the CAG length, and a multiplicative interaction term were investigated by multiple linear regression analysis for an association with IR, as indicated by homeostasis model assessment (HOMA %S). RESULTS: In a multivariate regression analysis adjusted for age and body mass index, free testosterone, CAG length, and a multiplicative interaction term were significantly associated with IR (P=0.001, P=0.001, P=0.01 respectively). The model explained 36.6% of the variation of IR and predicted that in carriers with a CAG length of 23, changes in testosterone would only minimally affect IR. For CAG lengths longer than 23, however, an increase in testosterone would improve IR, namely the longer the CAG length, the greater the effect. In contrast, in the case of CAG lengths shorter than 23, the effect of increasing testosterone would be the opposite. CONCLUSIONS: In men, testosterone and the AR CAG repeat length polymorphism interacted with respect to IR. The interpretation of the association between testosterone and IR seems to require consideration of the AR CAG repeat polymorphism. |
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Authors:
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Matthias Möhlig; Ayman M Arafat; Martin A Osterhoff; Frank Isken; Martin O Weickert; Joachim Spranger; Andreas F H Pfeiffer; Christof Schöfl |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-03-28 |
Journal Detail:
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Title: European journal of endocrinology / European Federation of Endocrine Societies Volume: 164 ISSN: 1479-683X ISO Abbreviation: Eur. J. Endocrinol. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-05-30 Completed Date: 2011-07-29 Revised Date: 2011-08-29 |
Medline Journal Info:
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Nlm Unique ID: 9423848 Medline TA: Eur J Endocrinol Country: England |
Other Details:
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Languages: eng Pagination: 1013-8 Citation Subset: IM |
Affiliation:
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Department of Endocrinology, Diabetes and Nutrition, Charité-University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. matthias.moehlig@charite.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Blood Glucose
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metabolism European Continental Ancestry Group Exons / genetics Gonadal Steroid Hormones / blood Heterozygote Humans Insulin Resistance / physiology* Male Middle Aged Obesity / genetics, metabolism Polymorphism, Genetic / genetics, physiology Receptors, Androgen / drug effects*, genetics* Regression Analysis Repetitive Sequences, Nucleic Acid Testosterone / blood, pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/AR protein, human; 0/Blood Glucose; 0/Gonadal Steroid Hormones; 0/Receptors, Androgen; 58-22-0/Testosterone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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