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Relationship between insulin release and /sup 65/zinc efflux from rat pancreatic islets maintained in tissue culture

Journal Article · · Diabetes; (United States)
OSTI ID:6848594
In short-term batch-incubation or perfusion experiments, we studied insulin release and associated /sup 65/Zn efflux from rat pancreatic islets loaded with /sup 65/Zn by 24-h tissue culture in low-glucose medium. The fractional basal insulin release and /sup 65/Zn efflux were 0.4% and 3% of total content/h/islet, respectively. Thus, basal /sup 65/Zn efflux was much greater than that to be accounted for if zinc was released proportionally with insulin release only; extragranular zinc flux was suggested. Two millimolar glucose, with or without 1 mM 3-isobutyl-1-methylxanthine (IBMX), affected neither insulin release nor associated /sup 65/Zn efflux. Twenty-five millimolar glucose produced a significant threefold increase in insulin release above baseline, but somewhat decreased /sup 65/Zn efflux at marginal significance. Glucose (25 mM) plus 1 mM IBMX provoked a high increase in insulin release and an associated 30% increase in fractional /sup 65/Zn efflux over basal. Calculations based on previous estimations of /sup 65/Zn distribution and equilibrium with islet zinc indicated that molar zinc efflux was more than sufficient to account for a 2-zinc-insulin hexamer. L-Leucine (2 or 20 mM) plus 1 mM IBMX caused far greater /sup 65/Zn efflux for the amount of insulin released, indicating additional /sup 65/Zn mobilization not directly related to insulin secretion. To evaluate /sup 65/Zn efflux during inhibited insulin secretion, batch incubations were performed in 100% D/sub 2/O or at 27 degrees C, conditions that inhibited insulin release stimulated by high glucose plus IBMX. These agents decreased the /sup 65/Zn efflux far below the basal value (35% and 50%, respectively) and greater than could be accounted for by the attendent inhibition of insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Research Organization:
Metabolic Research Unit, University of California, San Francisco
OSTI ID:
6848594
Journal Information:
Diabetes; (United States), Journal Name: Diabetes; (United States) Vol. 33:3; ISSN DIAEA
Country of Publication:
United States
Language:
English