| Project/Area Number |
24890219
|
|---|
| Research Category |
Grant-in-Aid for Research Activity Start-up
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | Jichi Medical University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2012-08-31 – 2014-03-31
|
| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 糖尿病 / インスリン分泌 / インクレチンホルモン / GLP-1 / 糖代謝 / GIP / EPAC / Trpm2 / 膵β細胞 / cAMP / exendin-4 / EPAC2 |
|---|
| Research Abstract |
In pancreatic beta-cells, closure of ATP-sensitive-K+ (K-ATP) channel is an initial process triggering glucose-stimulated insulin secretion. However theoretically, closure of K-ATP channel alone should be insufficient to shift membrane potential toward threshold level to set on insulin secretion. Opening of background nonselective-cation channels (NSCCs) facilitates excitability of the membrane. We here show that a class of NSCC is activated by both glucose and incretin hormones, GLP-1 and GIP, via cAMP/EPAC-mediated NSCC (TRPM2 channel) pathway. Our data demonstrate that glucose metabolism leads to opening of TRPM2 channel and closure of K-ATP channel simultaneously. Glucose- and incretin-activated NSCC works in concert to effectively induce membrane depolarization to initiate insulin secretions. The present study reveals a newly confirmed beta-cell mechanism through which glucose and incretin evoke insulin secretion and provides a innovative target to treat type 2 diabetes.
|
