S. Daniel et al., Identification of the docked granule pool responsible for the first phase of glucose-stimulated insulin secretion, DIABETES, 48(9), 1999, pp. 1686-1690
The mechanisms underlying the first phase of glucose-stimulated insulin rel
ease, the deterioration of which marks the early stages of both type 1 and
type 2 diabetes, are essentially unknown. Among many hypotheses, one holds
that the first phase is due to a readily releasable pool of insulin-contain
ing granules, We used current knowledge of the mechanisms of exocytosis and
the proteins involved in docking granules at the plasma membrane to test t
his hypothesis, A docked pool of readily releasable granules was identified
by immunoprecipitation of the plasma membrane protein syntaxin with a spec
ific antibody and by co-immunoprecipitation of soluble N-ethylmaleimide-sen
sitive factor attachment protein-25 (SNAP-25) and the granule proteins syna
ptobrevin and synaptotagmin. The four SNARE proteins co-immunoprecipitated
each other, thus identifying the core complex associated with docked granul
es, Using co-immunoprecipitation as a marker for docked granules, we found
that the docked pool was rapidly discharged during the first phase of gluco
se-stimulated insulin release and refilled during the second phase, Other s
ecretagogues also released the pool, whereas the physiological inhibitor no
repinephrine blocked its release. Further studies on the nature of this poo
l of granules should shed light on the causes of its deterioration in the e
arly stages of diabetes and the reasons for deficient insulin release.