Activation of protein kinase A (cAMP-dependent protein kinase; PKA) triggers insulin secretion in the β-cell. Adenylate cyclase toxin (ACT), a bacterial exotoxin with adenylate cyclase activity, and forskolin, an activator of adenylate cyclase, both dose-dependently increased insulin secretion in the presence, but not the absence, of glucose in insulin-secreting βTC3 cells. The stimulation of cAMP release by either agent was dose-dependent but glucose-independent. Omission of extracellular Ca2+ totally abolished the effects of ACT on insulin secretion and cytosolic cAMP accumulation. ACT and forskolin caused rapid and dramatic increases in cytosolic Ca2+, which were blocked by nifedipine and the omission of extracellular Ca2+. Omission of glucose completely blocked the effects of forskolin and partially blocked the effects of ACT on cytosolic Ca2+. PKA α, β and γ catalytic subunits (Cα, Cβ and Cγ respectively) were identified in βTC6 cells by confocal microscopy. Glucose and glucagon-like polypeptide-1 (GLP-1) caused translocation of Cα to the nucleus and of Cβ to the plasma membrane and the nucleus, but did not affect the distribution of Cγ. In conclusion, glucose and GLP-1 amplify insulin secretion via cAMP production and PKAβ activation.
Protein kinase A translocation and insulin secretion in pancreatic β-cells: studies with adenylate cyclase toxin from Bordetella pertussis
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Zhiyong GAO, Robert A. YOUNG, Matteo M. TRUCCO, Scott R. GREENE, Erik L. HEWLETT, Franz M. MATSCHINSKY, Bryan A. WOLF; Protein kinase A translocation and insulin secretion in pancreatic β-cells: studies with adenylate cyclase toxin from Bordetella pertussis. Biochem J 1 December 2002; 368 (2): 397–404. doi: https://doi.org/10.1042/bj20020999
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