Abstract
Swelling of secretory vesicles is critical for the regulated release of intra-vesicular contents from cells during secretion. At the secretory vesicle membrane of the exocrine pancreas and neurons, GTP-binding G proteins, vH+-ATPase, potassium channels and AQP water channels, are among the players implicated in vesicle volume regulation. Here we report in the endocrine insulin-secreting MIN6 cells, the similar requirement of vH+-ATPase-mediated intracellular acidification on glucose-stimulated insulin release. MIN6 cells exposed to the vH+-ATPase inhibitor Bafilomycin A show decreased acidification of the cytosolic compartment that include insulin-carrying granules. Additionally, a loss of insulin granules near the cell plasma membrane following Bafilomycin A treatment, suggests impaired transport of insulin granules and consequent decrease in glucose-stimulated insulin secretion and accumulation of intracellular insulin. These results suggest that vH+-ATPase-mediated intracellular acidification is required for insulin secretion in beta cells.
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Work presented in this article was supported in part by the WSU Interdisciplinary Biomedical Systems Fellowship.
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ARN and BPJ designed the experiments and wrote the manuscript. BJF, RGP and AL analyzed results and contributed to the methods section. We thank Won Jin Cho for his expert help with the figure illustration.All authors critically analyzed results and proof read the manuscript.
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Naik, A.R., Formosa, B.J., Pulvender, R.G. et al. vH+-ATPase-induced intracellular acidification is critical to glucose-stimulated insulin secretion in beta cells. Histochem Cell Biol 153, 279–285 (2020). https://doi.org/10.1007/s00418-019-01841-0
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DOI: https://doi.org/10.1007/s00418-019-01841-0