Human diabetes associated with defects in nuclear regulatory proteins for the insulin receptor gene

被引:32
作者
Brunetti, A
Brunetti, L
Foti, D
Accili, D
Goldfine, ID
机构
[1] UNIV REGGIO CALABRIA,FAC MED & CHIRURG,CATTEDRA ENDOCRINOL,I-88100 CATANZARO,ITALY
[2] UNIV CALIF SAN FRANCISCO,MT ZION MED CTR,DEPT MED,DIV DIABET & ENDOCRINE RES,SAN FRANCISCO,CA 94120
[3] NIDDKD,DIABET BRANCH,BETHESDA,MD 20892
关键词
insulin receptor; insulin resistance; non-insulin-dependent diabetes mellitus; gene transcription; trans-acting factors;
D O I
10.1172/JCI118400
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The control of gene transcription is mediated bq sequence-specific DNA-binding proteins (trans-acting factors) that bind to upstream regulatory elements (cis elements), We have previously identified two DNA-binding proteins that specifically interact with two unique AT-rich sequences of the 5' regulatory region of the insulin receptor gene which have in vivo promoter activity, Herein we have investigated the expression of these DNA-binding proteins in cells from two unrelated patients with insulin resistance and non-insulin-dependent diabetes mellitus. In these patients, the insulin receptor gene was normal. In EBV-transformed lymphoblasts from both patients, insulin receptor mRNA levels and insulin receptor expression were decreased. The expression of nuclear-binding proteins for the 5' regulatory region of the insulin receptor gene was markedly reduced, and this defect paralleled the decrease in insulin receptor protein expression. These studies indicate that DNA-binding proteins to the regulatory region of the insulin receptor gene are important for expression of the insulin receptor. Further, they suggest that in affected individuals, defects in the expression of these proteins may cause decreased insulin receptor expression and insulin resistance.
引用
收藏
页码:258 / 262
页数:5
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