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The role of protein kinase C in insulin biosynthesis

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Abstract

Activation of protein kinase C (PKC) by the phorbol ester 4β-phorbol myristate acetate (4β-PMA) stimulated (pro)insulin biosynthesis in collagenase-isolated rat islets of Langerhans, as assessed by measuring the incorporation of [35S]cysteine into proinsulin and insulin after fractionation by high performance liquid chromatography. The stimulatory effects of 4β-PMA were observed at a substimulatory concentration of glucose (2 mM) but were not additive to the stimulatory effects of 20 mM glucose on insulin biosynthesis. Prolonged exposure to 4β-PMA caused a marked down-regulation of PKC activity in islets. PKC-depleted islets showed a much reduced biosynthetic response to 20 mM glucose, but this was caused, at least in part, by an enhanced basal rate of (pro)insulin synthesis. These elevations in the basal rate of insulin synthesis were not secondary to an inerease in the amount of preproinsulin mRNA in PKC-depleted islets since Northern blot analysis showed that prolonged exposure to 4β-PMA, and the subsequent loss of PKC activity, did not detectably alter basal levels of preproinsulin mRNA. These results suggest that the activation of PKC stimulates (pro)insulin synthesis in rat islets by enhancing translation of existing preproinsulin mRNA, and that this may play some part in the biosynthetic responses of β-cells to glucose.

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Correspondence to S. J. Persaud.

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Gwilliam, D.J., Jones, P.M., Persaud, S.J. et al. The role of protein kinase C in insulin biosynthesis. Acta Diabetol 30, 99–104 (1993). https://doi.org/10.1007/BF00578222

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Key words

  • Insulin synthesis
  • Islet of Langerhans
  • Northern blotting
  • Phorbol ester
  • Protein kinase C