| First Author | Dubois MJ | Year | 2006 |
| Journal | Nat Med | Volume | 12 |
| Issue | 5 | Pages | 549-56 |
| PubMed ID | 16617349 | Mgi Jnum | J:109558 |
| Mgi Id | MGI:3629277 | Doi | 10.1038/nm1397 |
| Citation | Dubois MJ, et al. (2006) The SHP-1 protein tyrosine phosphatase negatively modulates glucose homeostasis. Nat Med 12(5):549-56 |
| abstractText | The protein tyrosine phosphatase SHP-1 is a well-known inhibitor of activation-promoting signaling cascades in hematopoietic cells but its potential role in insulin target tissues is unknown. Here we show that Ptpn6(me-v/me-v) (also known as viable motheaten) mice bearing a functionally deficient SHP-1 protein are markedly glucose tolerant and insulin sensitive as compared to wild-type littermates, as a result of enhanced insulin receptor signaling to IRS-PI3K-Akt in liver and muscle. Downregulation of SHP-1 activity in liver of normal mice by adenoviral expression of a catalytically inert mutant of SHP-1, or after small hairpin RNA-mediated SHP-1 silencing, further confirmed this phenotype. Tyrosine phosphorylation of CEACAM1, a modulator of hepatic insulin clearance, and clearance of serum [125I]-insulin were markedly increased in SHP-1-deficient mice or SHP-1-deficient hepatic cells in vitro. These findings show a novel role for SHP-1 in the regulation of glucose homeostasis through modulation of insulin signaling in liver and muscle as well as hepatic insulin clearance. |
