2012 Fiscal Year Final Research Report
Role of zinc transporters in beta-cell-autophagy induction
| Project/Area Number |
22590996
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | Juntendo University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
WATADA Hirotaka 順天堂大学, 医学部, 教授 (60343480)
|
|---|
| Project Period (FY) |
2010 – 2012
|
| Keywords | オートファジー / 亜鉛 / トランスポーター / 2型糖尿病 |
|---|
| Research Abstract |
Recent genome-wide association studies demonstrated that common variants of SLC30A8 increase susceptibility to type 2 diabetes. SLC30A8 encodes zinc transporter-8 (ZnT8), which delivers zinc ion from the cytoplasm into insulin granules. In this study, we generated ・-cell-specific Slc30a8-deficient mice, and demonstrated an unexpected functional linkage between Slc30a8 deletion and hepatic insulin clearance. The mutant mice had low peripheral blood insulin levels, despite insulin h ypersecretion from pancreatic ・ cells. In a series of experiments, we showed that a substantial amount of the hypersecreted insulin was degraded during its first passage through the liver. Consistent with these findings, slc30a8-deficient mice exhibited increased insulin clearance, as assessed by the c-peptide/insulin ratio. As one of the explanations for the above findings, we demonstrated that zinc cosecreted with insulin suppressed insulin clearance by inhibiting clathrin-dependent insulin endocytosis.
|
-
[Book] 亜鉛と糖尿病
Author(s)
福中彩子、藤谷与士夫
Total Pages
189-207
Publisher
建帛社
