Insulin signaling and glucose homeostasis in mice lacking protein tyrosine phosphatase alpha.
Studies in cultured cells have implicated protein tyrosine phosphatase alpha (PTPalpha) as a potential regulator of insulin signaling. The physiological role of PTPalpha in insulin action was investigated using gene-targeted mice deficient in PTPalpha. PTPalpha-null animals had normal body weights and circulating levels of glucose and insulin in random fed and fasted states. In glucose and insulin tolerance tests, their efficiency of blood glucose clearance was comparable to wild-type mice. Kinetics and extents of insulin-stimulated insulin receptor and IRS-1 tyrosine phosphorylation were similar in wild-type and PTPalpha(-/-) liver, muscle, and adipose tissue. However, the association of IRS-1 and PI 3-K was altered in PTPalpha(-/-) liver, with increased insulin-independent and reduced insulin-stimulated association compared to wild-type samples. This did not affect activation of the downstream signaling effector Akt. Our data indicate that PTPalpha is not a negative regulator of insulin signaling and does not perform an essential role in mediating the physiological action of insulin.
Le
Hoa T
HT
Department of Pathology and Laboratory Medicine, British Columbia Research Institute for Children's and Women's Health, University of British Columbia, V5Z 4H4 Vancouver, BC, Canada.
Ponniah
Sathivel
S
Pallen
Catherine J
CJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D004591:Electrophoresis, Polyacrylamide Gel; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D015151:Immunoblotting; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D015398:Signal Transduction; D013997:Time Factors; D014018:Tissue Distribution; D014443:Tyrosine / Q000378:metabolism
D001786:Blood Glucose; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; C516841:PTPRA protein, human; D017027:Protein Tyrosine Phosphatases; C516843:Ptpra protein, mouse; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D005947:Glucose