Cyclic AMP dynamics in the pancreatic beta-cell
2012 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 117, no 4, 355-369 p.Article, review/survey (Refereed) Published
Insulin secretion from pancreatic beta-cells is tightly regulated by glucose and other nutrients, hormones, and neural factors. The exocytosis of insulin granules is triggered by an elevation of the cytoplasmic Ca2+ concentration ([Ca2+](i)) and is further amplified by cyclic AMP (cAMP). Cyclic AMP is formed primarily in response to glucoincretin hormones and other G(s)-coupled receptor agonists, but generation of the nucleotide is critical also for an optimal insulin secretory response to glucose. Nutrient and receptor stimuli trigger oscillations of the cAMP concentration in beta-cells. The oscillations arise from variations in adenylyl cyclase-mediated cAMP production and phosphodiesterase-mediated degradation, processes controlled by factors like cell metabolism and [Ca2+](i). Protein kinase A and the guanine nucleotide exchange factor Epac2 mediate the actions of cAMP in beta-cells and operate at multiple levels to promote exocytosis and pulsatile insulin secretion. The cAMP signaling system contains important targets for pharmacological improvement of insulin secretion in type 2 diabetes.
Place, publisher, year, edition, pages
2012. Vol. 117, no 4, 355-369 p.
Epac2, insulin secretion, oscillations, protein kinase A
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-187231DOI: 10.3109/03009734.2012.724732ISI: 000310372800002OAI: oai:DiVA.org:uu-187231DiVA: diva2:574744