Abstract
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.
MeSH terms
-
Animals
-
Antigens, Surface / metabolism
-
Bacterial Proteins
-
Botulinum Toxins / genetics
-
Botulinum Toxins / pharmacology*
-
Calcium / pharmacology*
-
Cell Line
-
Cell Membrane Permeability
-
Cricetinae
-
Exocytosis / drug effects*
-
Gene Expression
-
Glucose / pharmacology*
-
Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
-
Humans
-
Insulin / metabolism*
-
Insulin Secretion
-
Islets of Langerhans / metabolism*
-
Membrane Proteins / metabolism
-
Nerve Tissue Proteins / metabolism
-
Potassium Chloride / pharmacology
-
R-SNARE Proteins
-
Recombinant Fusion Proteins
-
Streptolysins / pharmacology
-
Synaptosomal-Associated Protein 25
-
Syntaxin 1
-
Transfection
Substances
-
Antigens, Surface
-
Bacterial Proteins
-
Insulin
-
Membrane Proteins
-
Nerve Tissue Proteins
-
R-SNARE Proteins
-
Recombinant Fusion Proteins
-
SNAP25 protein, human
-
STX1A protein, human
-
Streptolysins
-
Synaptosomal-Associated Protein 25
-
Syntaxin 1
-
streptolysin O
-
Guanosine 5'-O-(3-Thiotriphosphate)
-
Potassium Chloride
-
Botulinum Toxins
-
botulinum toxin type C
-
Glucose
-
Calcium
-
botulinum toxin type E