Transient expression of botulinum neurotoxin C1 light chain differentially inhibits calcium and glucose induced insulin secretion in clonal beta-cells.
We have investigated the effect of botulinum neurotoxin (BoNT) C1 light chain (LC) on insulin exocytosis from the clonal beta-cell line HIT-T15. In streptolysin-O permeabilized cells, the beta-cell impermeant BoNT C1 cleaved mainly syntaxin 1 and inhibited Ca2+ as well as GTPgammaS induced exocytosis. To study the effect of BoNTs in intact cells, we transiently coexpressed the BoNT LC together with a reporter gene for insulin release. BoNT C1 inhibited K+ induced insulin secretion by 95% but reduced insulin release stimulated by glucose only by 25%. Thus a component of glucose stimulated insulin release is insensitive to BoNT C1.
Land
J
J
Département de Médecine Interne, Centre Médical Universitaire, Université de Genève, Geneva, Switzerland. Jochen.Lang@medecine.unige.ch
Zhang
H
H
Vaidyanathan
V V
VV
Sadoul
K
K
Niemann
H
H
Wollheim
C B
CB
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001426:Bacterial Proteins; D001905:Botulinum Toxins / Q000235:genetics / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D002463:Cell Membrane Permeability; D006224:Cricetinae; D005089:Exocytosis / Q000187:drug effects*; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D050683:R-SNARE Proteins; D011993:Recombinant Fusion Proteins; D013301:Streptolysins / Q000494:pharmacology; D050825:Synaptosomal-Associated Protein 25; D050827:Syntaxin 1; D014162:Transfection
D000954:Antigens, Surface; D001426:Bacterial Proteins; D007328:Insulin; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D011993:Recombinant Fusion Proteins; C494208:SNAP25 protein, human; C494212:STX1A protein, human; D013301:Streptolysins; D050825:Synaptosomal-Associated Protein 25; D050827:Syntaxin 1; C025964:streptolysin O; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D011189:Potassium Chloride; D001905:Botulinum Toxins; C096324:botulinum toxin type C; D005947:Glucose; D002118:Calcium; C096326:botulinum toxin type E