Analysis of protein regulating expression of insulin receptor gene.
| Project/Area Number |
02671099
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Osaka University |
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Principal Investigator |
KAWAMORI Ryuzo Osaka Univ. Dept of Med. Lecture, 医学部, 講師 (00116021)
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| Co-Investigator(Kenkyū-buntansha) |
WATARAI Takao Osaka Univ. Dept of Med. Researcher, 医学部付属病院, 医員
IWAMA Norimichi Osaka Univ. Dept of Med. Researcher, 医学部付属病院, 医員
MORISHIMA Toyohiko Osaka Univ. Dept of Med. Researcher, 医学部, 助手 (50221635)
YAMASAKI Yoshimitsu Osaka Univ. Dept of Med. Researcher, 医学部, 助手 (40201834)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1991: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1990: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Insulin Receptor / Expression / Gluco corticoid / グルココルチマイド / 培養リンパ球 / インスリン / レセプタ- / グルココルチコイド / 遺伝子発現調節 / Type A インスリン抵抗性 |
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| Research Abstract |
Mutations have been identified in the insulin-receptor gene in insulin-resistant patients. We studied two patients with acanthosis nigricans and insulin resistance caused by a decrease in the number of -cell surface insulin receptors. Patient 1 was an 11-yr-old boy with a fasting insulin level of 2130 PM ; patient 2 was a 14-yr-old girl with hyperandrogenism and a fasting insulin level of 580-740 pM. Based on Southern-blotting studies, the structure of both alleles of the insulin-receptor gene in both patients appeared to be grossly normal. There wag no evidence of insertions, deletions, or major rearrangements. Moreover, the nucleotide sequences of all 22 exons of the gene were normal in both patients. Thus, the predieted amino acid sequences of both patients' insulin receptors were normal. In Epstein-Barr virus-transformed lymphoblasts from patient 1, insulin-receptor mRNA levels were so low they could not be detected with an RNase A protection assay, whereas mRNA levels from patient
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2 were in the lower half of the normal range. By use of a more sensitive assay based on the polymerase chain reaction, insulin-receptor mRNA could be detected in Epstein-Barr virus-transformed lymphoblasts from both patients. Moreover, because of the existence of silent polymorphisms in the nucleotide sequences, it was possible to differentiate the two allele the two alleles of the insulin-receptor gene in both patients. In patient 2, the two alleles were expressed asymmetrically, with 90% of the mRNA molecules having been transcribed from one allele but only 10% transcribed from the second allele. This suggeststhat there is an unidentified mutation in the underexpressed allele that acts in cis-dominant fashion to decrease insulin-receptor mRNA levels. However, in patient 1, both alleles were expressed symmetrically in similarly low levels. Although not proven, it seems likely that the mutations that decrease insulin-receptor mRNA levels in patient 1 also map to the insulin-receptor locus. Less
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Report
(3 results)
Research Products
(12 results)
