Vias de sinalização da prolactina em ilhotas de Langerhans de ratos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2003

RESUMO

During pregnancy, panereatie islets undergo a number of structural and functional changes in response to an increased demand for insulin. These changes are orchestrated by several hormones including GH, plaeental lactogens, and prolactin (pRL). Many ofthe alterations observed during pregnancy ean be reproduced in vitro, especially if one uses neonatal islets as a model. The treatment of neonatal islets with PRL inereases: insulin synthesis, GLUT2 expression, glueokinase activity, glucose metabolism, eAMP metabolism, ATP produetion, ionic activity (represented by higher ability of the glueose in retaining K+ and Ca2+ inside the islet eells), and finally insulin secretion. Thus, taking into aeeount the pleiotropie effects of PRL on panereatie islets and reconsidering that PRL acts mainly via the JAK2/STATs pathways in most of the target tissues, we have studied here if PRL stimulates also the PI 3 kinase and MAPK pathways in islets ITom neonatal and ITom pregnant rats. Sinee insulin is important for the maintenance of the mass and functionality of adult islets, we have also analyzed a possible eross-talk between the signaling pathways of these two hormones. PRL signifieantly potentiated glueose-induced insulin secretion in islets cultured for 7 days. This effect was bloeked by the speeifie PI 3-kinase inhibitor, wortmannin. PRL treatment also reduced apoptosis that was accompanied by an inerease in Bad Ser 112 phosphorylation. These effects were abolished by wortmannin. PRL did not affeet mRNA expression of apoptotie protein sueh as Bad, Bax, and Bcl-XL. Similar to what was observed for insulin, the exposure of neonatal islets for short period of time (5 and 15 min) to PRL inereased, in a dose-dependent manner, IRS 1/2 tyrosine phosphorylation, their association with, and activation of PI 3-kinase. However, these effects were not additive to the effects of insulin. PRL also increased JAK2, SHC, ERK1/2 phosphoryIation in neonatal isIets. In pregnant rats (17th -19th days of pregnancy) higher IeveIs of tyrosine (IRS1, IRS2, SHC, ERK), serine (AKT), and serine-threonine (p70 S6-kinase) phosphorylation were found, compared to controIs. The treatment of pregnant rats with PRL receptor antisense (pRLR), but not sense oligonucIeotides, significantly reduced the expression of PRLR in uterus and islets, the expression of islet tyrosine phosphorylated proteins with molecu1ar masses of 250-160, 160-105 and 105-75 kDa, phosphorylation of the p70 S6-kinase and, finally, the glucose-induced insulin secretion. In conclusion, PRL treatment activates PI 3-kinase and MAPK pathways in neonatal islets. These pathways seem to be more active in islets ITom pregnant than controI rats. Since PRL induced phosphoryIation of Bad Ser 112, a preferential target for MAPK, was abolished by wortmannin, some earIy cross talk between the PI 3-kinase and MAPK cascades may occur during stimulation with PRL

ASSUNTO(S)

prolactina ilhotas de langerhans insulina

ACESSO AO ARTIGO

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