Modulation of IR/PTP1B interaction and downstream signaling in insulin sensitive tissues of MSG-rats.
PTP1B has been shown to be a negative regulator of the insulin signal transduction in insulin resistant states. Herein we investigated IR/PTP1B interaction and downstream signaling in insulin sensitive tissues of 10 and 28-week-old MSG-insulin resistant rats which represent different stages of insulin resistance. Our results demonstrated that the increase in PTP1B expression and/or association with IR in MSG animals may contribute to the impaired insulin signaling mainly in liver and muscle. Although, adipose tissue of 10-week-old MSG rats showed higher PTP1B expression and IR/PTP1B interaction, they were not sufficient to impair all insulin signaling since IRS-2 phosphorylation and association with PI3-kinase and Akt serine phosphorylation were increased, which may contribute for the increased adiposity of these animals. In 28-week-old-MSG rats there was an increase in IR/PTP1B interaction and reduced insulin signaling in liver, muscle and adipocytes, and a more pronounced insulin resistance.
Hirata
Aparecida Emiko
AE
Departamento de Clínica Médica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, FCM-UNICAMP, 13081-970 Campinas, SP, Brazil.
Alvarez-Rojas
Fernanda
F
Carvalheira
José Barreto Campello
JB
Carvalho
Carla Roberta de Oliveira
CR
Dolnikoff
Miriam Sterman
MS
Abdalla Saad
Mario José
MJ
D000273:Adipose Tissue / Q000737:chemistry / Q000378:metabolism; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000032:analysis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000502:physiology*; D015398:Signal Transduction; D012970:Sodium Glutamate / Q000008:administration & dosage*; D014443:Tyrosine / Q000378:metabolism
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011972:Receptor, Insulin; D012970:Sodium Glutamate; D014443:Tyrosine; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; C494920:Akt1 protein, rat; C516610:Ptpn1 protein, rat