Stimulation of insulin release from permeabilized HIT‐T15 cells by a synthetic peptide corresponding to the effector domain of the small GTP‐binding protein rab3

[摘要]

A synthetic peptide (rab3AL) corresponding to the effector domain of rab3, a small GTP-binding protein, stimulated basal and potentiated Ca²⁺-as well as GTPγS-evoked insulin secretion about 2-fold from streptolysin-O permeabilized HIT cells. This effect was specific, since the analogous peptides of ras or rab1 did not affect the exocytotic event. The more than additive effect of rab3AL on Ca²⁺ or GTPγS stimulation indicates a distinct mode of action of the peptide. The partial loss of cytosolic proteins from permeabilized cells was accompanied by a faster run-down of the secretory response to Ca²⁺ than the one to GTPγS. The persistent effect of rab3AL under these conditions points to a membrane localization of its target. These results suggest that rab3 and its effector are involved in the regulation of insulin secretion.

[学科分类] 生物化学/生物物理

[关键词] GTP-binding protein;Insulin secretion;Calcium;Rab protein;Exocytosis;G-protein;GTP-binding protein;SMGs;small molecular weight GTP-binding proteins;GAP;GTPase-activating protein;GDI;GDP-dissociation inhibitor;GDS;GDP-dissociation stimulator;GDPβS;guanosine 5'-O-(2-thiodiphosphate);GTPγS;guanosine-5'-O-(3-thiotrisphosphate);SL-O;streptolysin-O