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Expression of CD38 with intracellular enzymatic activity: a possible explanation for the insulin release induced by intracellular cADPR

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Abstract

CD38 is a transmembrane glycoprotein expressed in multiple cell types, including pancreatic β cells. It can serve as an enzyme that catalyzes the metabolism of two different Ca2+-mobilizing compounds, cyclic adenosine diphosphoribose (cADPR) and nicotinic acid adenine dinucleotide phosphate. One of these metabolites, cADPR, is known to be involved in glucose-induced insulin secretion from pancreatic β cells. Although the essential role of CD38 for endogenous cADPR synthesis has been established, the relationship between the proposed extracellular enzymatic activity of CD38 and the intracellular Ca2+ modulation caused by the intracellular cADPR accumulation has not yet been fully explained. For a better understanding of the role of CD38 in the insulin secretion machinery, analysis of the intracellular localization of this molecule in pancreatic β cells is essential. In an attempt to provide a method to probe the N-terminal and C-terminal of CD38 separately, we generated an insulin-secreting MIN6 murine pancreatic β cell line expressing a human CD38 bearing an N-terminal FLAG epitope tag. We found a weak but consistent expression of the FLAG epitope outside of the cells, indicating the presence of a small amount of CD38 with cytoplasmic enzymatic activity. MIN6 cells transfected with human CD38 exhibited increased glucose-induced insulin release. In addition, anti-FLAG cross-linking further enhanced the insulin release, suggesting that the N-terminal of CD38 expressed on the cell surface functions as a receptor for an unknown ligand and triggers positive signals for insulin secretion.

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Authors and Affiliations

  1. Department of Laboratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Yasuhiko Ohta, Akira Kitanaka & Tomohiko Taminato

  2. Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan

    Keichiro Mihara

  3. Division of Endocrinology and Metabolism, Hematology, Rheumatology, and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Osamu Imataki & Hiroaki Ohnishi

  4. Environmental Health Sciences, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Terukazu Tanaka

  5. Department of Transfusion Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Yoshitsugu Kubota

Authors
  1. Yasuhiko Ohta
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  2. Akira Kitanaka
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  8. Yoshitsugu Kubota
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Correspondence to Akira Kitanaka.

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Ohta, Y., Kitanaka, A., Mihara, K. et al. Expression of CD38 with intracellular enzymatic activity: a possible explanation for the insulin release induced by intracellular cADPR. Mol Cell Biochem 352, 293–299 (2011). https://doi.org/10.1007/s11010-011-0765-x

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  • DOI: https://doi.org/10.1007/s11010-011-0765-x

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