Clarification of genetic and pathogenic mechanism of insulin receptor abnormality

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K19602
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TAKASAWA Kei 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (50749463)
• Research Collaborator: TSUJI Atsumi (HOSOKAWA Atsumi) ; KASHIMADA Kenichi
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: インスリン受容体 / 糖尿病 / インスリン抵抗性 / インスリン受容体異常症 / 妖精症 / Ａ型インスリン抵抗症 / SGA

Outline of Final Research Achievements

We reported seven Japanese cases with clinically diagnosed insulin receptor (INSR) abnormality including one case with Leprechaunism and six peripubertal cases with clinically diagnosed type A IR. In five of seven cases, five INSR mutations including three novel mutations; S98R, G1146R, R1201P, and two previously reported mutations; R1158W, R1201W, were identified. We also demonstrated that reduced mRNA expression of INSR should be considered as a possible cause of insulin resistance. By a group comparative study between INSR mutation-positive and mutation-negative cases, we indicated common clinical features of type A insulin resistance with the INSR mutations which were family history of diabetes mellitus and absence of fatty liver. Furthermore, being small for gestational age is another clinical feature of type A insulin resistance with the INSR mutation.

Free Research Field

小児内分泌学