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Action Potential-Induced Ca2+ Influx for Both Acute and Sustained Insulin Secretion in Pancreatic Beta Cells

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Neurosecretion: Secretory Mechanisms

Part of the book series: Masterclass in Neuroendocrinology ((MANEURO,volume 8))

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Abstract

Insulin is a key molecule to maintain glucose hemostasis in the body. In pancreatic beta cells, insulin secretion is triggered by Ca2+ and amplified by cAMP/PKA signaling pathway. In the past few years, several studies have shown that these two signaling pathways are coupled with each other, although the causal relationship between them is still obscure. By combining FRET imaging and electrophysiological methods, a recent report confirms the role of Ca2+ to activate cAMP/PKA pathway through adenylyl cyclase 8 (AC8), a Ca2+-stimulated AC isoform. Simultaneous recordings of PKA activity and insulin granule exocytosis suggest the dual roles of Ca2+ in insulin secretion: to trigger acute exocytosis directly and to maintain sustained insulin secretion via cAMP/PKA. Here, we briefly summarize the roles of Ca2+, cAMP/PKA, and adenylyl cyclase in glucose/GLP-1-mediated insulin secretion and the unique method used in these studies.

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Acknowledgments

We thank Li Zhou, Hongping Huang, Quanfeng Zhang, Younus M. Khan, and Changhe Wang for helpful comments. This work was supported by grants from the National Natural Science Foundation of China (31228010, 31171026, 31100597, 31327901, 31221002, 31330024, 31670843, 31521062, and 31400708) and the National Key Research and Development Program of China (2016YFA0500401).

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Authors and Affiliations

  1. State Key Laboratory of Membrane Biology, Peking University, Beijing, China

    Haiqiang Dou & Zhuan Zhou

  2. Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China

    Haiqiang Dou & Zhuan Zhou

  3. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China

    Haiqiang Dou & Zhuan Zhou

  4. PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China

    Haiqiang Dou & Zhuan Zhou

  5. Department of Physiology, Sahlgrenska Academy, Institute of Neuroscience and Physiology, University of Gothenburg, Göteborg, Sweden

    Haiqiang Dou

Authors
  1. Haiqiang Dou
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  2. Zhuan Zhou
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Correspondence to Haiqiang Dou .

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Editors and Affiliations

  1. Medical School, University of Massachusetts, Worcester, MA, USA

    José R. Lemos

  2. Molecular Mechanisms in Neurodegenerative Diseases Laboratory, MMDN, University of Montpellier, EPHE, INSERM, UMR-S1198, Montpellier, France

    Govindan Dayanithi

Key References: See Main List for Reference Details

Key References: See Main List for Reference Details

  • Ammala et al. (1993). The role of cAMP/PKA pathway to potentiate insulin secretion was demonstrated for the first time in pancreatic beta cells.

  • Dou et al. (2015). This paper revealed the dual roles of Ca2+ in regulating insulin secretion, to trigger exocytosis directly, and to replenish pools of insulin granules via the AC-cAMP/PKA pathway.

  • Dyachok et al. (2008). Real-time monitoring of glucose-induced cAMP oscillation in beta cells was achieved in this paper.

  • Ozaki et al. (2000). A Ca2+-cAMP-PKA circuit was studied thoroughly in pancreatic beta cells, by using a unique FRET-based PKA indicator, AKAR3.

  • Von RĂĽden and Neher (1993). The role of Ca2+ to replenish vesicle pools was first studied in this paper.

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Dou, H., Zhou, Z. (2020). Action Potential-Induced Ca2+ Influx for Both Acute and Sustained Insulin Secretion in Pancreatic Beta Cells. In: Lemos, J., Dayanithi, G. (eds) Neurosecretion: Secretory Mechanisms. Masterclass in Neuroendocrinology, vol 8. Springer, Cham. https://doi.org/10.1007/978-3-030-22989-4_8

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