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Adenine Nucleotides in the Secretory Granule Fraction of Rat Islets¹

Departments of Medicine (Endocrinology), Pharmacology, and Pathology, University of Colorado School of Medicine and Veterans Administration Hospital Denver, Colorado 80220

Abstract

Concomitant with glucose-induced insulin release, there occurred an increase of ATP from 4.40 ± 0.21 to 23.16 ± 0.52 pmol/100 islets/min (P < 0.001) in the effluent from perifused rat islets. There is a linear relationship between circulating ATP and insulin levels both in the stimulated and basal state (r = 0.689, P < 0.01). Islets incubated with labeled adenine for a short period of time (37.5 min) showed no release of radioactivity upon subsequent glucose-induced insulin release. Islets incubated for a prolonged interval with labeled adenine (150 min) showed an increase in acid soluble radioactivity in the effluent during glucoseinduced insulin release. Following incubation of the islets with labeled adenine for 150 min, approximately 5% of the homogenate radioactivity was found in the secretory granules. Using column chromatography to separate the adenine nucleotides, the distribution of radioactivity among the various nucleotides in the secretory granule fraction was found to be: AMP 54.42 ± 4.96%, ADP 14.20 ± 1.63%, ATP 15.39 ± 3.84%, and cAMP 16.07 ± 2.11%. The distribution of radioactivity in the effluent adenine nucleotides after glucose-induced insulin release was: AMP 32.83 ± 4.62%, ADP 24.52 ± 2.77%, ATP 28.13 ± 5.45%, and cAMP 26.01 ± 3.34%. The absolute levels of adenine nucleotides in the secretory granules were ATP 4.19 ± 0.88, ATP + ADP 7.94 ± 2.20 and cAMP 4.46 ± 1.74 pmol/ug prot. The levels in the islet effluent were ATP, 15.30 ± 2.70, ATP + ADP, 29.43 ± 3.49 and cAMP 7.66 ± 1.93 pmol/100 islets/ min for the first ten min of glucose-stimulated insulin release. Thereafter there was a rapid decline in effluent cAMP while ATP and ADP remained in essentially equivalent amounts. The distribution of radioactivity and absolute levels of the adenine nucleotides in the effluent reflects that found in the secretory granules, confirming previous observations that insulin release is occurring by exocytosis.(Endocrinology 95: 662, 1975)

Footnotes

¹ This work was supported by Veterans Research Service Funds (MRIS 8227-01) and grants from Upjohn and Ciba-Geigy Companies. A preliminary report of some of this work was presented at the 33rd Annual Meeting of the American Diabetes Association, Chicago, Illinois, June 23, 1974.

² Department of Pharmacology, Emory University, School of Medicine, Atlanta, Georgia 30322.

Received June 28, 1974.

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