Obesity Research Today is a free monthly online journal that collates and summarizes the latest research about Obesity, including details on health, diet, prevention, exercise.

Reduction of low molecular weight protein-tyrosine phosphatase expression improves hyperglycemia and insulin sensitivity in obese mice.

Pandey SK, Yu XX, Watts LM, Michael MD, Sloop KW, Rivard AR, Leedom TA, Manchem VP, Samadzadeh L, McKay RA, Monia BP, Bhanot S

Metabolic Disease Program, Antisense Drug Discovery, Isis Pharmaceuticals, Carlsbad, CA 92008, USA. spandey@isisph.com

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.

Published 7 May 2007 in J Biol Chem, 282(19): 14291-9.
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