Impaired expression of transcription factor IUF1 in a pancreatic β‐cell line derived from a patient with persistent hyperinsulinaemic hypoglycaemia of infancy (nesidioblastosis)

FEBS Letters

Aynsley-Green, Albert²  Read, Martin L¹  James, Roger F.L³  Macfarlane, Wendy M¹  Cragg, Helen¹  Docherty, Hilary M¹  Docherty, Kevin¹ 

[1] Department of Molecular and Cell Biology, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK;Institute of Child Health, The University of London, 30 Guildford Street, London WC1N 1EH, UK;Department of Surgery, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX, UK

关键词: Insulin gene;    Transcription;    Islet of Langerhans;    Nesidioblastosis;    Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI);    PHHI;    persistent hyperinsulinaemic hypoglycaemia of infancy;    EMSA;    electrophoretic mobility shift assay;    TKp;    thymidine kinase promoter;   

DOI  :  10.1016/S0014-5793(97)00874-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI), or nesidioblastosis, is a rare disorder which may be familial or sporadic, and which is characterized by unregulated secretion of insulin and profound hypoglycaemia in the neonate. The defect has been linked in some patients to mutations in the sulphonyl urea receptor gene (SUR). The present study investigated potential defects in the regulation of the insulin gene by glucose in a β-cell line (NES 2Y) derived from a patient with PHHI. The results show that the insulin promoter is unresponsive to glucose in PHHI, and that this defect can be attributed to impaired expression of the transcription factor IUF1. Because IUF1 is involved not only in linking glucose metabolism to the control of the insulin, but is also a major regulator of β-cell differentiation during embryogenesis, we propose that impaired expression of IUF1 contributes to β-cell dysfunction in PHHI by leading to abnormal β-cell differentiation.

【 授权许可】

Unknown