Loading...
Please wait, while we are loading the content...
Similar Documents
Parathyroid Hormone–Related Protein Induces Insulin Expression Through Activation of MAP Kinase–Specific Phosphatase-1 That Dephosphorylates c-Jun NH2-Terminal Kinase in Pancreatic β-Cells
| Content Provider | Paperity |
|---|---|
| Author | Ogata, Masato Sawada, Yoshie Hosaka, Masahiro Torii, Seiji Takeuchi, Toshiyuki Izumi, Tetsuro Mizutani, Shin Zhang, Bin |
| Abstract | Parathyroid hormone–related protein (PTHrP) increases the content and mRNA level of insulin in a mouse β-cell line, MIN6, and primary-cultured mouse islets. We examined the mechanism of PTHrP-induced insulin expression. The PTHrP effect was markedly augmented by SB203580, a mitogen-activated protein (MAP) kinase inhibitor, and SB203580 itself increased insulin expression extensively, even without PTHrP. Because SB203580 inhibits both p38 and c-jun NH2-terminal kinases (JNKs), we investigated the JNK-specific inhibitor SP600125. SP600125 also increased insulin content and its mRNA level. PTHrP induced dephosphorylation of JNK1/2, and PTHrP-induced insulin expression was blocked by a dominant-negative type JNK-APF. We suspected that dual specificity MAP kinase phosphatases (MKPs) may be involved in the PTHrP-induced insulin expression by inactivating JNK1/2. MIN6 cells contained at least five MKPs, among which only MKP-1 was inducible by PTHrP. PTHrP-induced insulin expression was blocked by the MKP-1 expression inhibitor Ro-31-8220, indicating that the PTHrP effect is mediated by MKP-1. Indeed, adenoviral MKP-1 expression increased insulin expression by decreasing a phosphorylation form of JNKs and a resulting phosphorylated form of c-jun in MIN6 cells. The phosphorylated form of c-jun is known to repress cAMP-dependent insulin gene promoter activity. Thus, MKP-1 controls the insulin expression by downregulating a JNK/c-jun pathway. |
| Starting Page | 2720 |
| Ending Page | 2730 |
| File Format | HTM / HTML |
| ISSN | 00121797 |
| DOI | 10.2337/diabetes.52.11.2720 |
| Issue Number | 11 |
| Journal | Diabetes |
| Volume Number | 52 |
| e-ISSN | 1939327X |
| Language | English |
| Publisher | American Diabetes Association |
| Publisher Date | 2003-11-01 |
| Access Restriction | Open |
| Subject Keyword | Erk, extracellular signal-regulated kinase Gapdh, glyceraldehyde-6-phosphate dehydrogenase Moi, multiplicity of infection Jip, c-jun nh2-terminal kinase–interacting protein Mkp, map kinase–specific protein phosphatase Glp, glucagon-like polypeptide Pka, protein kinase a Pthrp, parathyroid hormone–related protein Map, mitogen-activated protein Jnk, c-jun nh2-terminal kinase Iri, immunoreactive insulin Pkc, protein kinase c |
| Content Type | Text |
| Resource Type | Article |
| Subject | Endocrinology, Diabetes and Metabolism Internal Medicine |
