The phosphatidylinositol/AKT/atypical PKC pathway is involved in the improved insulin sensitivity by DHEA in muscle and liver of rats in vivo.
DHEA improves insulin sensitivity and has anti-obesity effect in animal models and men. However, the molecular mechanisms by which DHEA improves insulin action have not been clearly understood. In the present study, we examined the protein levels and phosphorylation state of insulin receptor (IR), IRS-1 and IRS-2, the association between IRSs and PI3K and SHP2, the insulin-induced IRSs associated PI 3-kinase activities, and the phosphorylation status of AKT and atypical PKCzeta/lambda in the liver and the muscle of 6 month-old Wistar rats treated with DHEA. There was no change in IR, IRS-1 and IRS-2 protein levels in both tissues of treated rats analysed by immunoblotting. On the other hand, insulin-induced IRS-1 tyrosine phosphorylation was increased in both tissues while IRS-2 tyrosyl phosphorylation was increased in liver of DHEA treated group. The PI3-kinase/AKT pathway was increased in the liver and the PI3K/atypical PKCzeta/lambda pathway was increased in the muscle of DHEA treated rats. These data indicate that these regulations of early steps of insulin action may play a role in the intracellular mechanism for the improved insulin sensitivity observed in this animal model.
Campbell
Carmen S G
CS
Departamento de Fisiologia e Biofísica, ICB1, USP, São Paulo, SP, Brasil, Caixa Postal, CEP05389-970, Brazil.
Caperuto
Luciana C
LC
Hirata
A Emiko
AE
Araujo
Eliana P
EP
Velloso
Licio A
LA
Saad
Mario J
MJ
Carvalho
Carla R O
CR
D000818:Animals; D001786:Blood Glucose; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D015151:Immunoblotting; D007328:Insulin / Q000378:metabolism* / Q000502:physiology; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008099:Liver / Q000378:metabolism; D008297:Male; D018832:Molecular Chaperones / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta
D001786:Blood Glucose; D003687:Dehydroepiandrosterone; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D018832:Molecular Chaperones; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D000099293:Protein Kinase C-lambda; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; C490392:Prkcz protein, rat; D000099221:Protein Kinase C zeta; C494920:Akt1 protein, rat