2018 Fiscal Year Final Research Report
Pathophysiological role of ghrelin in impaired GLP-1 secretion in tyte 2 diabetes
| Project/Area Number |
15K09397
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | Jichi Medical University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2015-10-21 – 2019-03-31
|
| Keywords | インスリン分泌 / 糖代謝 / 糖尿病 |
|---|
| Outline of Final Research Achievements |
On the basis of intestinal GLP-1 action that potentiates glucose-induced insulin release, incretin-based medicines have been widely used to treat type 2 diabetic patients. Gastric hormone ghrelin, in contrast, attenuates GLP-1-potentiated insulin release and GLP-1 release. GLP-1 and ghrelin are released in a reciprocal pattern. Therefore, the increased ghrelin/GLP-1 ratio in preprandial periods effectively prevents hypoglycemia and induces appetite. In contrast, the decreased ghrelin/GLP-1 ratio in postprandial periods effectively induces satiety and promotes disposal of elevated blood glucose. The interplay of ghrelin and GLP-1 may play a role in the systemic control of feeding and glucose metabolism, providing a novel strategy to treat type 2 diabetes with impaired insulin release and obesity with hyperphagia.
|
| Free Research Field |
糖尿病学、内分泌学
|
| Academic Significance and Societal Importance of the Research Achievements |
血中グレリン濃度は、食前に高値を示し食後速やかに低下する。一方、GLP-1はグレリンと正反対の血中動態を示し、食後、小腸から分泌されインスリン分泌を促進する。糖尿病ではGLP-1分泌が低下しており、インスリン分泌不全の一因と考えられているが、その病態生理は未解明である。本研究で、グレリンがGLP-1分泌を抑制していることが示され、糖尿病の病因解明の新たな布石となることが期待される。グレリン阻害によるGLP-1分泌促進とGLP-1作用増強は、GLP-1関連薬の効果を増強する新たなコンセプトによるインスリン分泌促進薬の開発基盤となり得る。
|
