PMID- 10480595
OWN - NLM
STAT- MEDLINE
DCOM- 19990930
LR  - 20191210
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 48
IP  - 9
DP  - 1999 Sep
TI  - Identification of the docked granule pool responsible for the first phase of
      glucose-stimulated insulin secretion.
PG  - 1686-90
AB  - The mechanisms underlying the first phase of glucose-stimulated insulin release, 
      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-containing granules.
      We used current knowledge of the mechanisms of exocytosis and the proteins
      involved in docking granules at the plasma membrane to test this hypothesis. A
      docked pool of readily releasable granules was identified by immunoprecipitation 
      of the plasma membrane protein syntaxin with a specific antibody and by
      co-immunoprecipitation of soluble N-ethylmaleimide-sensitive factor attachment
      protein-25 (SNAP-25) and the granule proteins synaptobrevin and synaptotagmin.
      The four SNARE proteins co-immunoprecipitated each other, thus identifying the
      core complex associated with docked granules. Using co-immunoprecipitation as a
      marker for docked granules, we found that the docked pool was rapidly discharged 
      during the first phase of glucose-stimulated insulin release and refilled during 
      the second phase. Other secretagogues also released the pool, whereas the
      physiological inhibitor norepinephrine blocked its release. Further studies on
      the nature of this pool of granules should shed light on the causes of its
      deterioration in the early stages of diabetes and the reasons for deficient
      insulin release.
FAU - Daniel, S
AU  - Daniel S
AD  - Department of Molecular Medicine, College of Veterinary Medicine, Cornell
      University, Ithaca, New York 14853-6401, USA.
FAU - Noda, M
AU  - Noda M
FAU - Straub, S G
AU  - Straub SG
FAU - Sharp, G W
AU  - Sharp GW
LA  - eng
GR  - R01-DK-42063/DK/NIDDK NIH HHS/United States
GR  - R01-DK-54243/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Insulin)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Peptides)
RN  - 0 (Wasp Venoms)
RN  - 660YQ98I10 (Potassium Chloride)
RN  - 72093-21-1 (mastoparan)
RN  - IY9XDZ35W2 (Glucose)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cytoplasmic Granules/*physiology
MH  - Exocytosis/physiology
MH  - *Glucose
MH  - Insulin/*metabolism
MH  - Insulin Secretion
MH  - Intercellular Signaling Peptides and Proteins
MH  - Islets of Langerhans/cytology/drug effects/metabolism
MH  - Membrane Proteins/physiology
MH  - Norepinephrine/physiology
MH  - Peptides
MH  - Potassium Chloride/pharmacology
MH  - Stimulation, Chemical
MH  - Wasp Venoms/pharmacology
EDAT- 1999/09/10 00:00
MHDA- 1999/09/10 00:01
CRDT- 1999/09/10 00:00
PHST- 1999/09/10 00:00 [pubmed]
PHST- 1999/09/10 00:01 [medline]
PHST- 1999/09/10 00:00 [entrez]
AID - 10.2337/diabetes.48.9.1686 [doi]
PST - ppublish
SO  - Diabetes. 1999 Sep;48(9):1686-90. doi: 10.2337/diabetes.48.9.1686.