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⁶⁵Zinc and Endogenous Zinc Content and Distribution in Islets in Relationship to Insulin Content^*

D. P. FIGLEWICZ, S. E. FORHAN, A. T. HODGSON and G. M. GRODSKY

Metabolic Research Unit, Department of Biochemistry and Biophysics, University of California San Francisco San Francisco, California 94143

Address all correspondence and requests for reprints to: Gerold M. Grodsky, Ph.D., Metabolic Research Unit, HSW 1157, University of California, San Francisco, California 94143.

Abstract

Uptake of ⁶⁵Zn and distribution of ⁶⁵Zn, total zinc, and insulin were measured in rat islets and islet granules under different conditions of islet culture. Specific activity of islet zinc (⁶⁵Zn/zinc) was less than 15% that of extracellular zinc even after 48 h. In contrast, once in the islet, ⁶⁵Zn approached 70% of equilibrium with granular zinc in 24 h and apparent equilibrium by 48 h. During a 24-h culture, at either high or low glucose, reduction of both islet zinc and insulin occurred. However, zinc depletion was greater than that predicted if zinc loss was proportional to insulin depletion and occurred only from the granular compartment, which represents only one third of the total islet zinc. Extension of culture to 48 h caused additional insulin depletion, but islet zinc was unchanged. Omission of calcium during the 48-h culture caused a predicted increase in insulin retention, presumably by inhibiting secretion; however, zinc retention was not increased proportionately. Pretreatment of rats with tolbutamide caused a massive depletion of insulin stored in isolated islets, with little change in total islet zinc; subsequent culture of these islets resulted in a greater loss of granular zinc than predicted from the small loss of granular insulin. None of the conditions tested affected the precentage of either ⁶⁵Zn or total zinc that was distributed in the islet granules. Results show that 1) zinc exists in a metabolically labile islet compartment(s) as well as in secretory granules; and 2) extra-granular zinc, although not directly associated with insulin storage, may act as a reservoir for granular zinc and may regulate insulin synthesis, storage, and secretion in ways as yet unknown. (Endocrinology 115: 877–881, 1984)

Footnotes

^* This work was supported in part by NIH Grant AM-01410 and a gift from Kenneth and Gloria Levy of Saratoga, CA.

Recipient of a grant from the Achievement Rewards of College Scientists, Inc., Northern California Chapter.

Received February 1, 1984.

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