Inhibition of the protein tyrosine phosphatase PTPIB: Potential therapy for obesity, insulin resistance and type-2 diabetes mellitus

被引：220

作者：

Koren, Shlomit ^{[6
]}

Fantus, I. George ^{[1
,2
,3
,4
,5
]}

机构：

[1] Univ Toronto, Dept Physiol & Med, Toronto, ON M5T 3L9, Canada

[2] Univ Toronto, Div Endocrinol & Metab, Toronto, ON M5T 3L9, Canada

[3] Univ Toronto, Mt Sinai Hosp, Univ Hlth Network, Dept Med, Toronto, ON M5T 3L9, Canada

[4] Univ Toronto, Univ Hlth Network, Toronto Gen Res Inst, Banting & Best Diabet Ctr, Toronto, ON M5T 3L9, Canada

[5] Univ Toronto, Dept Physiol, Univ Hlth Network, Toronto, ON M5T 3L9, Canada

[6] Univ Toronto, Dept Med, Univ Hlth Network, Toronto, ON, Canada

来源：

BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM | 2007年 / 21卷 / 04期

基金：

加拿大健康研究院;

关键词：

protein tyrosine phosphatases; insulin signalling; PTPIB; type-2; diabetes; mellitus; leptin;

D O I：

10.1016/j.beem.2007.08.004

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The global epidemic of obesity and type-2 diabetes mellitus (T2DM) has highlighted the need for new therapeutic approaches. The association of insulin resistance with these disorders and the knowledge that insulin receptor signaling is mediated by tyrosine (Tyr) phosphorylation have generated great interest in the regulation of the balance between Tyr phosphorylation and dephosphorylation. Several protein Tyr phosphatases (PTPs) have been implicated in the regulation of insulin action, with the most convincing data for PTPIB. Murine models targeting PTPIB, PTPIB-/- mice, demonstrate enhanced insulin sensitivity without the weight gain seen with other insulin sensitizers such as peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists, probably due to a second action of PTP I B as a negative regulator of leptin signaling. Despite intensive efforts and recent progress, a safe, selective and efficacious PTP I B inhibitor has yet to be identified.

引用

页码：621 / 640

页数：20

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