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A single nucleotide polymorphism in STK11 influences insulin sensitivity and metformin efficacy in hyperinsulinemic girls with androgen excess.

ABSTRACT: OBJECTIVE: Serine-threonine kinase STK11 catalyzes the AMP-activated protein kinase complex. We tested the hypothesis that a gene variant in STK11 contributes to variation in insulin sensitivity and metformin efficacy. RESEARCH DESIGN AND METHODS: We studied the effects of a single nucleotide polymorphism (SNP) (rs8111699) in STK11 on endocrine-metabolic and body composition indexes before and after 1 year of metformin in 85 hyperinsulinemic girls with androgen excess, representing a continuum from prepuberal girls with a combined history of low birth weight and precocious pubarche over to postmenarchial girls with hyperinsulinemic ovarian hyperandrogenism. Metformin was dosed at 425 mg/day in younger girls and 850 mg/day in older girls. STK11 rs8111699 was genotyped. Endocrine-metabolic features were assessed in the fasting state; body composition was estimated by absorptiometry. RESULTS: Genotype effects were similar in younger and older girls. At baseline, the mutated G allele in STK11 rs8111699 was associated with higher insulin and IGF-I levels (both P < 0.005). The response to metformin differed by STK11 genotype: GG homozygotes (n = 24) had robust metabolic improvements, GC heterozygotes (n = 38) had intermediate responses, and CC homozygotes (n = 23) had almost no response. Such differences were found for 1-year changes in body composition, circulating insulin, IGF-I, free androgen index, and lipids (all P < 0.005). CONCLUSIONS: In hyperinsulinemic girls with androgen excess, the STK11 rs8111699 SNP influences insulin sensitivity and metformin efficacy, so that the girls with the least favorable endocrine-metabolic profile improve most with metformin therapy.

SUBMITTER: Lopez-Bermejo A

PROVIDER: S-EPMC2890356 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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A single nucleotide polymorphism in STK11 influences insulin sensitivity and metformin efficacy in hyperinsulinemic girls with androgen excess.

López-Bermejo Abel A Díaz Marta M Morán Erica E de Zegher Francis F Ibáñez Lourdes L Ibáñez Lourdes L

Diabetes care 20100331 7

<h4>Objective</h4>Serine-threonine kinase STK11 catalyzes the AMP-activated protein kinase complex. We tested the hypothesis that a gene variant in STK11 contributes to variation in insulin sensitivity and metformin efficacy.<h4>Research design and methods</h4>We studied the effects of a single nucleotide polymorphism (SNP) (rs8111699) in STK11 on endocrine-metabolic and body composition indexes before and after 1 year of metformin in 85 hyperinsulinemic girls with androgen excess, representing ...[more]

PMID: 20357370

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Dataset Information

A single nucleotide polymorphism in STK11 influences insulin sensitivity and metformin efficacy in hyperinsulinemic girls with androgen excess.

Publications

A single nucleotide polymorphism in STK11 influences insulin sensitivity and metformin efficacy in hyperinsulinemic girls with androgen excess.

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