vH -ATPase-induced intracellular acidification is critical to glucose-stimulated insulin secretion in beta cells.

Naik, Akshata R.; Formosa, Brent J.; Pulvender, Rishika G.; Liyanaarachchi, Asiri G.; Jena, Bhanu P.

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.

PANCREATIC beta cells; INSULIN; SECRETORY granules; SECRETION; G proteins; POTASSIUM channels; ADENOSINE triphosphatase

Histochemistry & Cell Biology, 2020, Vol 153, Issue 4, p279

0948-6143

Academic Journal

10.1007/s00418-019-01841-0