2004 Fiscal Year Final Research Report Summary
Research on the genes that are expressed in beta-cells and affect the insulin promoter
| Project/Area Number |
13671199
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | JICHI MEDICAL SCHOOL |
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Principal Investigator |
TAMEMOTO Hiroyuki Jichi Medical School, Dept. of Medicine, Lecturer, 医学部, 講師 (90292630)
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| Project Period (FY) |
2001 – 2004
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| Keywords | PPARγ |
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| Research Abstract |
In search of genes that enhance the insulin promoter activity, the effects of HNF4 α, FOXO1 and peroxisome proliferator-activated receptor γ(PPAR γ) were analyzed. Each constract was co-transfected to cultured beta-cell, Min6 cells with the rat-insulin promoter-luciferase reporeter. HNF4 α inhibited the insulin promoter activity. This result was presented in Japan Diabetes Society Meeting in 2001. The dominant active mutant FOXO1 was made and it also inhibited the insulin promoter activity. This result was presented in the annual scientific session of American Diabetes Association (ADA) in 2001. The negative dominant mutant of PPAR γ (P467L) was made and it enhanced the insulin promoter acitivity. To analyze the in vivo effect of this mutation, an attempt to make transgenic mice was started. The mutant PPAR γ gene was inserted under CAG promoter separated by a loxP flanked neomycine resistance gene. Mice carrying this transgene were made. By crossing these mice with Cre recombinase transgenic mice, mutant PPAR gene will be expressed in tissues expressing Cre recombinase. Also, to analyze the impact of PPAR polymorphism on clinical aspects of diabetic patients, genomic samples were collected from 390 patients. The Pro12Ala polymorphism had no relation to nephropathy but carriers of this polymorphism had slightly smaller BMI. This result will be presented in ADA meeting this year. Analysis on eNOS and estrogen receptor alpha gene polymorphism using these samples were already presented in ADA meeting 2004.
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