Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Syp is a protein tyrosine phosphatase implicated in insulin and growth factor signaling. To evaluate the role of syp in insulin's regulation of plasma glucose, we generated knockout mice. Homozygous knockout mice die prior to day 10.5 of embryonic development. Hemizygous mice express half the levels of syp protein compared with their wild type littermates but do not display any gross morphological changes. Total body weight (age 2-10 weeks) and plasma insulin and glucose levels both in fasting and glucose-challenged states were comparable in the wild type and the hemizygous mice. No differences were observed in insulin-induced glucose uptake in soleus muscle and epididymal fat; insulin inhibition of lipolysis was also similar. We injected insulin into the portal vein of the mice to examine upstream events of the insulin signaling cascade. Tyrosine phosphorylation of insulin receptor and insulin receptor substrate-1 (IRS-1) from hemizygous tissue was similar to that of wild type tissue. Association of the p85 subunit of phosphatidylinositol 3-kinase to IRS-1 increased an average of 2-fold in both groups. We did not observe an increase of IRS-1/syp association after insulin administration, but we did note a significant basal association in both wild type and hemizygous tissue. Our results do not support a major role for syp in the acute in vivo metabolic actions of insulin.
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PMID:Insulin signaling in mice expressing reduced levels of Syp. 870 15

Plasma membranes of caput and cauda epididymal spermatozoa of hamster exhibited protein phosphatase activity. This membrane-associated protein phosphatase was identified as a protein tyrosine phosphatase based on its ability to hydrolyse a substrate specific for PTPase, by inhibition of its activity with a specific inhibitor of PTPase (sodium orthovanadate) and by the inability to inhibit its activity with calyculin, okadaic acid, trifluoperazine, calcium, EGTA, and EDTA, which are specific inhibitors of other protein phosphatases, namely PP-1, PP-2A, PP-2B, and PP-2C respectively. The specific activity of the protein tyrosine phosphatase both in the caput and cauda epididymal sperm plasma membranes was similar, implying that the enzyme may not be solely responsible for the differential phosphorylation of membrane proteins observed during maturation (Uma Devi et al. 1997. Mol Reprod Dev 47:341-350). Thus the significance of the PTPase activity in epididymal maturation still remains to be determined. The membrane-associated PTPase may not be essential for acquisition of motility. However, it appears that the activity is essential for the sustenance of motility since sodium orthovanadate, which specifically inhibits PTPase activity, also inhibits motility of spermatozoa and decreases the overall velocity of the spermatozoa by decreasing the average path velocity, straight line velocity, curvilinear velocity, and amplitude of lateral head displacement of the treated spermatozoa.
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PMID:Plasma membrane-associated protein tyrosine phosphatase activity in hamster spermatozoa. 1023 Aug 15

Recently, we have shown that a newly synthesized vanadyl complex, bis(1-oxy-2-pyridinethiolato)oxovanadium(IV), VO(opt)(2), is a potent orally active insulin-mimetic in treating streptozotocin-induced diabetes in rats, with long-term action. In the present study, the anti-diabetic effect of VO(opt)(2) and its mechanism in ob/ob mice, an obese non-insulin-dependent diabetes mellitus (NIDDM) animal model, was investigated. In ob/ob mice, 15-day oral treatment with VO(opt)(2) resulted in a dose-dependent decrease in the levels of glucose, insulin and triglyceride in blood. VO(opt)(2) was also effective in ameliorating impaired glucose tolerance in ob/ob mice, when an oral glucose tolerance test was performed after treatment with VO(opt)(2). Tumor necrosis factor-alpha (TNF-alpha) is a key component of obesity-diabetes link, we therefore examined the attenuating effect of VO(opt)(2) on impaired insulin signal transduction induced by TNF-alpha. Elevated expression of TNF-alpha was observed in the epididymal and subcutaneous fat tissues of ob/ob mice. Incubation of 3T3-L1, mouse adipocytes, with TNF-alpha reduced the phosphorylation of insulin receptor substrate-1 (IRS-1), whereas VO(opt)(2) treatment resulted in an enhancement of IRS-1 phosphorylation, irrespective of the presence or absence of TNF-alpha. Overall, the present study demonstrates that VO(opt)(2) exerts an anti-diabetic effect in ob/ob mice by ameliorating impaired glucose tolerance, and furthermore, attenuates the TNF-alpha-induced decrease in IRS-1 phosphorylation in adipocytes. These results suggest that the anti-diabetic action of VO(opt)(2) is derived from an attenuation of a TNF-alpha induced impaired insulin signal transduction via inhibition of protein tyrosine phosphatase, providing a potential clinical utility for VO(opt)(2) in the treatment of NIDDM.
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PMID:Amelioration of insulin resistance in diabetic ob/ob mice by a new type of orally active insulin-mimetic vanadyl complex: bis(1-oxy-2-pyridinethiolato)oxovanadium(IV) with VO(S(2)O(2)) coordination mode. 1141 Feb 38