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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1986-9-17
pubmed:abstractText
A new sequential gating perifusion technique was employed to investigate secretion vesicle margination and granule lysis in islets isolated from 2- and 18-month-old Fischer 344 rats. The technique is based on sequential perifusion (periods A, B, and C) of isolated islets with glucose (30, 165, or 300 mg/dl) in the presence of sodium isethionate, an inhibitor of granule lysis, followed thereafter by trifluoperazine, an inhibitor of secretion vesicle margination, and glucose (300 mg/dl) or isobutylmethylxanthine (IBMX; 400 microM). When glucose was employed during period A to marginate secretion vesicles to the plasma membrane, subsequent glucose- and IBMX-induced insulin release (period C) was depressed in islets from 18-month-old rats [maximal increase above the basal rate of release (delta max), 9 +/- 2 nU/micron X min] compared to that in the 2-month-old animals (delta max, -19 +/- 3 nU/micron X min). With glyburide (400 microM) used to induce secretion vesicle margination, glucose- and IBMX-induced insulin release was the same in young and old animals (delta max, 14 +/- 3 and 15 +/- 3 nU/micron X min, respectively). Insulin release was then studied as a function of secretion vesicle margination at the plasma membrane by measuring somatostatin (SRIF) receptor recruitment. The islets from older animals must be stimulated with 300 mg/dl glucose to attain the same level of SRIF binding as in islets isolated from younger animals stimulated with 150-165 mg/dl glucose. Insulin release per unit SRIF binding was identical in young and old animals (65 and 69 nU/liter fmol SRIF binding), indicating normal lysis of marginated secretion granules. These studies implicate glucose-induced secretion vesicle margination as the site of impairment in age-related insulin release.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
119
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
827-32
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
1986
pubmed:articleTitle
Insulin secretion in aging: studies with sequential gating of secretion vesicle margination and lysis.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't