title: Cyclic AMP dynamics in the pancreatic β-cell.
abstract: Insulin secretion from pancreatic β-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 Ca(2+) concentration ([Ca(2+)](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 β-cells. The oscillations arise from variations in adenylyl cyclase-mediated cAMP production and phosphodiesterase-mediated degradation, processes controlled by factors like cell metabolism and [Ca(2+)](i). Protein kinase A and the guanine nucleotide exchange factor Epac2 mediate the actions of cAMP in β-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.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Biomedical Centre , Box 571, SE-751 23 Uppsala, Sweden. anders.tengholm@mcb.uu.se
authors.forename: Anders
authors.initials: A
authors.lastname: Tengholm
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D007328:Insulin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D005947:Glucose