The nuclear receptor coactivator AIB3 is a modulator of HOMA beta-cell function in nondiabetic children.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Our results suggest that AIB3 contributes to the maintenance of beta-cell function in nondiabetic children and regulates gene expression in INS-1 cells.
Burghardt
Hans
H
Institute for Research in Biomedicine (IRB), Barcelona, Spain.
López-Bermejo
Abel
A
Baumgartner
Bernhard
B
Ibáñez
Lourdes
L
Vendrell
Joan
J
Ricart
Wifredo
W
Palacín
Manuel
M
Fernández-Real
José Manuel
JM
Zorzano
Antonio
A
D000818:Animals; D001724:Birth Weight / Q000235:genetics; D016022:Case-Control Studies; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism; D005865:Gestational Age; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D015810:Linkage Disequilibrium; D051379:Mice; D008954:Models, Biological; D056918:Nuclear Receptor Coactivators; D020641:Polymorphism, Single Nucleotide / Q000502:physiology
D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; C486559:NCOA6 protein, human; D056918:Nuclear Receptor Coactivators