Effects of protein kinase C activation on the regulation of the stimulus-secretion coupling in pancreatic β-cells

P. Arkhammar, T. Nilsson, M. Welsh, N. Welsh, P. O. Berggren

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Effects of protein kinase C (PKC) activation on the insulin-secretory process were investigated, by using β-cell-rich suspensions obtained from pancreatic islets of obese-hyperglycaemic mice. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), which is known to activate PKC directly, the muscarinic-receptor agonist carbamoylcholine and high glucose concentration enhance the phosphorylation of a specific 80 kDa PKC substrate in the β-cells. At a non-stimulatory glucose concentration, 10 nM-TPA increased insulin release, although there were no changes in either the cytoplasmic free Ca2+ concentration ([Ca2+](i)) or membrane potential, as measured with the fluorescent indicators quin-2 and bisoxonol respectively. At a stimulatory glucose concentration TPA caused a lowering in [Ca2+](i), whereas membrane potential was unaffected. Despite the decrease in [Ca2+](i), there was a large stimulation of insulin release. Addition of TPA lowered [Ca2+](i) also in β-cells stimulated by tolbutamide or high K+, although to a lesser extent than in those stimulated by glucose. There was no effect of TPA on either Ca2+ buffering or the ability of Ins(1,4,5)P3 to release Ca2+ in permeabilized β-cells. However, the phorbol ester inhibited the rise in [Ca2+](i) in response to carbamoylcholine, which stimulates the formation of InsP3, in intact β-cells. Down-regulation of PKC influenced neither glucose-induced insulin release nor the increase in [Ca2+](i). Hence, although PKC activation is of no major importance in glucose-stimulated insulin release, this enzyme can serve as a modulator of the glucose-induced insulin-secretory response. Such a modulation involves mechanisms promoting both amplification of the secretory response and lowering of [Ca2+](i).

Original languageEnglish (US)
Pages (from-to)207-215
Number of pages9
JournalBiochemical Journal
Issue number1
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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