PTP1B antisense-treated mice show regulation of genes involved in lipogenesis in liver and fat.

Abstract	Protein tyrosine phosphatases are important regulators of insulin signal transduction. Our studies have shown that in insulin resistant and diabetic ob/ob and db/db mice, reducing the levels of protein tyrosine phosphatase 1B (PTP1B) protein by treatment with a PTP1B antisense oligonucleotide resulted in improved insulin sensitivity and normalized plasma glucose levels. The mechanism by which PTP1B inhibition improves insulin sensitivity is not fully understood. We have used microarray analysis to compare gene expression changes in adipose tissue, liver and muscle of PTP1B antisense-treated ob/ob mice. Our results show that treatment with PTP1B antisense resulted in the downregulation of genes involved in lipogenesis in both fat and liver, and a downregulation of genes involved in adipocyte differentiation in fat, suggesting that PTP1B antisense acts through a different mechanism than thiazolidinedione (TZD) treatment. In summary, microarray results suggest that reduction of PTP1B may alleviate hyperglycemia and enhance insulin sensitivity by a different mechanism than TZD treatment.
Authors	Jeffrey F Waring, Rita Ciurlionis, Jill E Clampit, Sherry Morgan, Rebecca J Gum, Robert A Jolly, Paul Kroeger, Leigh Frost, James Trevillyan, Bradley A Zinker, Michael Jirousek, Roger G Ulrich, Cristina M Rondinone
Journal	Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 203 Issue 1-2 Pg. 155-68 (May 30 2003) ISSN: 0303-7207 [Print] Ireland
PMID	12782412 (Publication Type: Journal Article)
Chemical References	Blood Glucose Lipids Oligonucleotides, Antisense Protein Tyrosine Phosphatase, Non-Receptor Type 1 Protein Tyrosine Phosphatases Ptpn1 protein, mouse
Topics	Adipose Tissue (cytology, metabolism) Animals Blood Glucose (drug effects) Cell Differentiation (drug effects) Down-Regulation (drug effects) Gene Expression Profiling Gene Expression Regulation (drug effects) Insulin Resistance Lipids (biosynthesis) Liver (metabolism) Mice Mice, Obese Muscles (metabolism) Oligonucleotides, Antisense (pharmacology, therapeutic use) Protein Tyrosine Phosphatase, Non-Receptor Type 1 Protein Tyrosine Phosphatases (antagonists & inhibitors, physiology)

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