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PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice
Open accessAbstract
The role of protein-tyrosine phosphatase 1B (PTP1B) in diabetes was investigated using an antisense oligonucleotide in ob / ob and db / db mice. PTP1B antisense oligonucleotide treatment normalized plasma glucose levels, postprandial glucose excursion, and HbA 1C . Hyperinsulinemia was also reduced with improved insulin sensitivity. PTP1B protein and mRNA were reduced in liver and fat with no effect in skeletal muscle. Insulin signaling proteins, insulin receptor substrate 2 and phosphatidylinositol 3 (PI3)-kinase regulatory subunit p50α, were increased and PI3-kinase p85α expression was decreased in liver and fat. These changes in protein expression correlated with increased insulin-stimulated protein kinase B phosphorylation. The expression of liver gluconeogenic enzymes, phosphoenolpyruvate carboxykinase, and fructose-1,6-bisphosphatase was also down-regulated. These findings suggest that PTP1B modulates insulin signaling in liver and fat, and that therapeutic modalities targeting PTP1B inhibition may have clinical benefit in type 2 diabetes.
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Cited by
SIRT1 Improves Insulin Sensitivity under Insulin-Resistant Conditions by Repressing PTP1B
Sun, C., Zhang, F., Ge, X., Yan, T., Chen, X., Shi, X., & Zhai, Q. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.08.014 · Cited by 766
Biochemical and cellular properties of insulin receptor signalling
Haeusler, R. A., McGraw, T. E., & Accili, D. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.89 · Cited by 739
Neuronal PTP1B regulates body weight, adiposity and leptin action
Bence, K. K., Delibegovic, M., Xue, B., Gorgun, C. Z., Hotamisligil, G. S., Neel, B. G., & Kahn, B. B. (2006) · Nature Medicine · doi:10.1038/nm1435 · Cited by 633
Insulin signaling in health and disease
Saltiel, A. R. (2021) · Journal of Clinical Investigation · doi:10.1172/jci142241 · Cited by 446
Chemistry and Biochemistry of Type 2 Diabetes
Ross, S. A., Gulve, E. A., & Wang, M. (2004) · Chemical Reviews · doi:10.1021/cr0204653 · Cited by 323
Metadata
- Authors
- Zinker, B. A., Rondinone, C. M., Trevillyan, J. M., Gum, R. J., Clampit, J. E., Waring, J. F., Xie, N., Wilcox, D., Jacobson, P., Frost, L., Kroeger, P. E., Reilly, R. M., Koterski, S., Opgenorth, T. J., Ulrich, R. G., Crosby, S., Butler, M., Murray, S. F., McKay, R. A., Bhanot, S., Monia, B. P., & Jirousek, M. R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-08-08
- Volume
- 99
- Issue
- 17
- Pages
- 11357-11362
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2169218609
- Cited by
- 414
- References
- 0
- FWCI
- 9.29
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Zinker, B. A., Rondinone, C. M., Trevillyan, J. M., Gum, R. J., Clampit, J. E., Waring, J. F., Xie, N., Wilcox, D., Jacobson, P., Frost, L., Kroeger, P. E., Reilly, R. M., Koterski, S., Opgenorth, T. J., Ulrich, R. G., Crosby, S., Butler, M., Murray, S. F., McKay, R. A., . . . Jirousek, M. R. (2002). PTP1B antisense oligonucleotide lowers PTP1B protein, normalizes blood glucose, and improves insulin sensitivity in diabetic mice. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.142298199
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