How pancreatic beta-cells discriminate long and short timescale cAMP signals.

Biophysical Journal
Bradford E Peercy, Arthur S Sherman

Abstract

The translocation of catalytic protein kinase A (cPKA) in response to cyclic-adenosine mono-phosphate (cAMP) depends on the pattern of stimulus applied to the cell. Experiments with IBMX have shown that 1), sustained cAMP elevation is more effective than oscillations of cAMP at getting cPKA into the nucleus; and 2), cPKA enters the nucleus by diffusion. We constructed mathematical models of cAMP activation of cPKA and their diffusion in order to study nuclear translocation of cPKA, and conclude that hindered diffusion of cPKA through the nuclear membrane by a rapid-binding process, but not globally reduced diffusion, can explain the experimental data. Perturbation analysis suggests that normal physiological oscillations of glucose would not result in nuclear translocation, but chronically high glucose that produces extended calcium plateaus and/or chronic glucagonlike peptide-1 stimulation could result in elevated levels of nuclear cPKA.

References

Sep 1, 1974·Proceedings of the National Academy of Sciences of the United States of America·J A BeavoE G Krebs
Jul 1, 1994·Biophysical Journal·J Wagner, J Keizer
Aug 26, 1998·Annual Review of Nutrition·P B DanielJ F Habener
Feb 3, 1999·Annals of the New York Academy of Sciences·J J HolstL Bjerre-Knudsen
Oct 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·T C RichJ W Karpen
Mar 14, 2002·Current Opinion in Cell Biology·Manuela ZaccoloTullio Pozzan
Nov 27, 2002·Annals of Biomedical Engineering·Thomas C Rich, Jeffrey W Karpen
Aug 9, 2003·Diabetologia·N J Pyne, B L Furman
Dec 6, 2003·Science·Morris F White
Nov 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Lisa M DiPilatoJin Zhang
Aug 5, 2005·Journal of Cell Science·Lorene K Langeberg, John D Scott
Feb 16, 2006·Journal of Cell Science·Debbie Willoughby, Dermot M F Cooper
Aug 11, 2006·American Journal of Physiology. Cell Physiology·Thomas C RichMarco Conti
Aug 15, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey J SaucermanAndrew D McCulloch
Sep 13, 2006·PLoS Computational Biology·Maria LindskogJeanette Hellgren Kotaleski
Sep 16, 2006·The Journal of Physiology·George G HolzOleg G Chepurny
Feb 20, 2007·Pharmacology & Therapeutics·Máire E Doyle, Josephine M Egan
Oct 12, 2007·American Journal of Physiology. Cell Physiology·Leonid E FridlyandLouis H Philipson
Dec 17, 2008·Pharmacological Reviews·Wook Kim, Josephine M Egan

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Citations

May 4, 2017·Diabetes, Obesity & Metabolism·Anders Tengholm, Erik Gylfe
Mar 9, 2017·American Journal of Physiology. Endocrinology and Metabolism·Abdul Bari MuhammadXianxin Hua

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