PTP1B antisense-treated mice show regulation of genes involved in lipogenesis in liver and fat.
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.
Waring
Jeffrey F
JF
Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6123, USA. jeff.waring@abbott.com
Ciurlionis
Rita
R
Clampit
Jill E
JE
Morgan
Sherry
S
Gum
Rebecca J
RJ
Jolly
Robert A
RA
Kroeger
Paul
P
Frost
Leigh
L
Trevillyan
James
J
Zinker
Bradley A
BA
Jirousek
Michael
M
Ulrich
Roger G
RG
Rondinone
Cristina M
CM
D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007333:Insulin Resistance; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008820:Mice, Obese; D009132:Muscles / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology* / Q000627:therapeutic use; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*
D001786:Blood Glucose; D008055:Lipids; D016376:Oligonucleotides, Antisense; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516609:Ptpn1 protein, mouse