The nuclear receptor coactivator AIB3 is a modulator of HOMA β‐cell function in nondiabetic children

Abstract

The amplified in breast cancer-3 protein (AIB3) is a nuclear coactivator involved in proliferation, apoptosis and development. AIB3 loss of function causes deficient insulin secretion in mice, indicating that AIB3 participates in beta-cell regulation. Our objective was to evaluate genetic variants located on AIB3 associated with beta-cell function in children and to analyse the effect of AIB3 overexpression on gene expression in insulin 1 (INS-1) beta-pancreatic cells. Polymorphisms from AIB3 were genotyped in 148 children with normal or low birthweights for gestational age. The effect of AIB3 overexpression on gene expression was analysed by real-time polymerase chain reaction (PCR) in INS-1 cells. AIB3 variants were associated with homeostasis model assessment of beta-cell function (HOMA-beta-cell) in children with normal or low birthweights for gestational age, but not with HOMA of insulin resistance (HOMA-IR), or with birthweight. AIB3 overexpression increased the expression of genes involved in signalling, such as IRS-1, IRS-2, IGF-II receptor or Foxo1, or of genes that control insulin secretion, such as Cplx2, Glut2 or Kv3.1 in INS-1 cells. Our results suggest that AIB3 contributes to the maintenance of beta-cell function in nondiabetic children and regulates gene expression in INS-1 cells.