2018 Fiscal Year Final Research Report
Investigation of regulatory mechanisim of GIP secretion by fatty-acid binding protein 5 (FABP5)
| Project/Area Number |
16K09778
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Keywords | インクレチン分泌 |
|---|
| Outline of Final Research Achievements |
We examined FABP5 localization in K-cells before and after oral fat intakeusing electron microscopy and confocal microscopy.FABP5 was present both in the nucleus and in the cytoplasm of K-cells before loading. In contrast, 60 minutes after fat loading, the intranuclear localization has disappeared. The expression of Regulator of G protein signaling 4 (RGS4) was found to be elevated in the K cells of FABP5-deficient mouse. We clarified that both GPR120 and GPR40 are involved in GIP secretion after fat intake. Based on our results, it is suggested that GPR40 expressed in K-cells directly sense LCFA, and in contrast, GPR120 expressed in I-cells indirectly regulates GIP secretion in the presence of bile via CCK secretion.
|
| Free Research Field |
糖尿病・代謝
|
| Academic Significance and Societal Importance of the Research Achievements |
肥満・2型糖尿病患者の数は増加の一途をたどっており、全世界的に重要な健康問題であるが、有効かつ安全性の高い治療法は未だ確立されていないのが現状である。本研究で注目しているGIPはその治療標的として大変有望であり、その制御に関わる重要な分子としてFABP5に着目し、作用機構の解明に着手している。本研究の結果、薬剤によるFABP5の阻害が脂肪誘導性GIP分泌や脂肪摂取時の体重増加を抑制することが明らかとなれば、FABP5を標的とした肥満症の新たな治療法の開発、創薬につながることが期待され研究の意義は大きい。
|
