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Review

Recent advances in protein tyrosine phosphatase 1B inhibitors

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Pages 199-214 | Published online: 02 Mar 2005

Bibliography

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  • ••The seminal study on PTP1B-knockoutmice. This work provides the most compelling evidence supporting PTP1B as a downregulator of insulin signalling and the development of PTP1B inhibitors as therapeutics for treating Type 2 diabetes and obesity.
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  • ••An independent PTP1B knockout-mousestudy that confirms the results of Elchebly et[13]. These workers also report thattheir knockout mice exhibited an increase in metabolic rate and oxygen consumption, which may explain their resistance to diet-induced obesity. However, authors of the earlier study [13] have recently reported that no difference in oxygen consumption was observed in their knockout mice [2]. They suggest that expressing oxygen consumption as 02/ min/kg, as in [14], does not accurately reflect the measure of metabolic rate because it includes the metabolic inactive fat [2].
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  • ••This paper, along with [17], providescompelling evidence that PTP1B dephosphorylates Jak-2 and negatively regulates leptin signalling.
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  • ••See [16].
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  • •A recent review on the key advances in the characterisation of the structure, regulation and function of PTP1B, and illustrates how the understanding of the properties of this enzyme has revealed principles that apply to the PTP family as a whole.
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  • XIE L, LEE SY, ANDERSEN JN et al.: Cellular effects of small molecule PTP1B inhibitors on insulin signaling. Biochemist?), (2003) 42:12792–12804.
  • •Although the data in [86] suggests that compound 45 and PTP1B colocalise in the ER, no control experiment was run using a compound with similar hydrophobic properties that was not a PTP1B inhibitor. It is very possible that such a compound would also localise in the same regions of the cell.
  • ZINKER BA, RONDINONE CM, TREVILLYAN JM et al.: PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice. Proc. Natl. Acad. Sci. USA (2002) 99:11357–11362.
  • ••This report and references [88-90] describe some of the effects of a PTP1B ASO on glucose and fat metabolism.
  • GUM RJ, GAEDE LL, KOTERSKI SL et al.: Reduction of protein tyrosine phosphatase 1B increases insulin-dependent signaling in ob/ob mice. Diabetes (2003) 52:21–28.
  • RONDINONE CM, TREVILLYAN JM, CLAMPIT Jet al.: Protein tyrosine phosphatase 1B reduction regulates adiposity and expression of genes involved in lipogenesis. Diabetes (2002) 51:2405–2411.
  • WARING JF, CIURLIONIS R, CLAMPIT JE et al.: PTP1B antisense-treated mice show regulation of genes involved in lipogenesis in liver and fat. Mal Cell Endocrinol (2003) 203:155–168.

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