Reduction of Low Molecular Weight Protein-tyrosine Phosphatase Expression Improves Hyperglycemia and Insulin Sensitivity in Obese Mice
| Autor: | Amber R. Rivard, Xing Xian Yu, Sanjay K. Pandey, Thomas A. Leedom, Robert Mckay, Lynnetta Watts, Laura Samadzadeh, Kyle W. Sloop, Vara Prasad Manchem, M. Dodson Michael, Sanjay Bhanot, Brett P. Monia |
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| Rok vydání: | 2007 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Insulin Receptor Substrate Proteins medicine.medical_treatment Blotting Western Mice Obese Type 2 diabetes Biology Carbohydrate metabolism Biochemistry Mice Phosphatidylinositol 3-Kinases Insulin resistance Proto-Oncogene Proteins Internal medicine medicine Animals Immunoprecipitation Insulin Obesity Phosphorylation Molecular Biology Protein kinase B Glucose tolerance test medicine.diagnostic_test Body Weight Cell Biology Glucose Tolerance Test Oligonucleotides Antisense Phosphoproteins medicine.disease Receptor Insulin Isoenzymes Mice Inbred C57BL Insulin receptor Endocrinology Hyperglycemia Hepatocytes biology.protein Insulin Resistance Protein Tyrosine Phosphatases Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 282:14291-14299 |
| ISSN: | 0021-9258 |
| Popis: | To investigate the role of low molecular weight protein-tyrosine phosphatase (LMW-PTP) in glucose metabolism and insulin action, a specific antisense oligonucleotide (ASO) was used to reduce its expression both in vitro and in vivo. Reduction of LMW-PTP expression with the ASO in cultured mouse hepatocytes and in liver and fat tissues of diet-induced obese (DIO) mice and ob/ob mice led to increased phosphorylation and activity of key insulin signaling intermediates, including insulin receptor-beta subunit, phosphatidylinositol 3-kinase, and Akt in response to insulin stimulation. The ASO-treated DIO and ob/ob animals showed improved insulin sensitivity, which was reflected by a lowering of both plasma insulin and glucose levels and improved glucose and insulin tolerance in DIO mice. The treatment did not decrease body weight or increase metabolic rate. These data demonstrate that LMW-PTP is a key negative regulator of insulin action and a potential novel target for the treatment of insulin resistance and type 2 diabetes. |
| Databáze: | OpenAIRE |
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