Modulação da secreção de insulina em ilhotas de Langerhans pela crotoxina-like de Crotalus durissus collilineatus e suas subunidades

AUTOR(ES)
DATA DE PUBLICAÇÃO

2002

RESUMO

The crotoxin results from phospholipase A2 (PLA2) and crotapotin interaction. The PLA: acts in the membrane phospholipids generating arachidonic acid (AA). Venom PLA2 has been used as a pharmacological tool to identify target protein, mammalian receptor, and physiological cellular function. Therefore, the aim of this work was to study the role of crotoxin-like from Crotalus durissus colfjfjneatus and its subunits on the insulin secretion of the isolated rat Langerhans islets. Also, we investigated the underlying mechanisms by which the venom PLA2 would evoke insulin secretion in the presence of insulinotropic agents. Our experiments demonstrated that insulin secretion was potentialized by crotoxin in a dose-dependent manner in presence of low and high glucose concentration and this effect is related to PLA2. Neither glucose metabolism nor ionic channels (Ca+2 and Na+ channels) are involved in the enhancement of insulin secretion induced by PLA2 in isolated Langerhans islets since label glucose, nifedipine (10 mM) and tetrodotoxin (10 mM) did not affect this response. EGT A also did not interfere with the potentiation of insulin secretion induced PLA2 showing that extracellular calcium is not directly involved in this phenomenon. However, heparin and dexametasone significantly attenuated the increase of insulin secretion in response to PLA2.Moreover, the efflux of AA was markedly increased in parallel to enhancement of insulin secretion in isolated rat Langerhans islets. In conclusion, these findings show that the potentiation of insulin secretion induced by PLA2 in presence of glucose may be related to AA mobilization of Langerhans islets from rats

ASSUNTO(S)

insulina crotoxina langerhans fosfolipases ilhotas de

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