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Regulation of Cytoplasmic Free Ca2+ in Insulin-Secreting Cells

  • Chapter
New Concepts in the Pathogenesis of NIDDM

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 334))

Abstract

The cytoplasmic free Ca2+ concentration([Ca2+]i) has a fundamental role in the β-cell stimulus-secretion coupling and is regulated by a sophisticated interplay between nutrients, hormones and neurotransmitters. Metabolism of glucose and other nutrients leads to ATP generation, closure of ATP-regulated K+-channels, depolarization, opening of voltage-activated L-type Ca2+-channels, increase in [Ca2+]i and insulin release (1,2). Hormones and neurotransmitters affect the β-cell through the activation of receptors coupled to various effector systems, such as the adenylate cyclase (AC) or phospholipase C (PLC) system (2). Upon activation of these systems, cAMP is formed or phosphatidyl inositol 4,5-bisphosphate is hydrolysed, resulting in the formation of inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). Whereas InsP3 mobilizes intracellularly bound Ca2+, most probably from the endoplasmic reticulum, DAG activates protein kinase C (PKC) (1–3). Although InsP3 increases [Ca2+]i, there is little effect on insulin release, suggesting that the trisphosphate is not primarily involved as a signal for exocytosis in the β-cell (3). With regard to PKC, the physiological role is more clear and this enzyme is involved as a modulator of multiple steps in the β-cell signal-transduction pathway (1–3).

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Authors and Affiliations

  1. Department of Endocrinology, Karolinska Institute, The Rolf Luft Center for Diabetes Research, Stockholm, Sweden

    Per-Olof Berggren, Per Arkhammar, Md Shahidul Islam, Lisa Juntti-Berggren, Akhtar Khan, Henrik Kindmark, Martin Köhler, Kerstin Larsson, Olof Larsson, Thomas Nilsson, Åke Sjöholm, Jaroslaw Szecowka & Qimin Zhang

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    Claes Göran Östenson  & Suad Efendić  & 

  2. University of Toronto, Toronto, Ontario, Canada

    Mladen Vranic

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Berggren, PO. et al. (1993). Regulation of Cytoplasmic Free Ca2+ in Insulin-Secreting Cells. In: Östenson, C.G., Efendić, S., Vranic, M. (eds) New Concepts in the Pathogenesis of NIDDM. Advances in Experimental Medicine and Biology, vol 334. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2910-1_3

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