title: Glucose and GLP-1 stimulate cAMP production via distinct adenylyl cyclases in INS-1E insulinoma cells.
abstract: In beta cells, both glucose and hormones, such as GLP-1, stimulate production of the second messenger cAMP, but glucose and GLP-1 elicit distinct cellular responses. We now show in INS-1E insulinoma cells that glucose and GLP-1 produce cAMP with distinct kinetics via different adenylyl cyclases. GLP-1 induces a rapid cAMP signal mediated by G protein-responsive transmembrane adenylyl cyclases (tmAC). In contrast, glucose elicits a delayed cAMP rise mediated by bicarbonate, calcium, and ATP-sensitive soluble adenylyl cyclase (sAC). This glucose-induced, sAC-dependent cAMP rise is dependent upon calcium influx and is responsible for the glucose-induced activation of the mitogen-activated protein kinase (ERK1/2) pathway. These results demonstrate that sAC-generated and tmAC-generated cAMP define distinct signaling cascades.
authors.affiliation: Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Lavoisier S
authors.initials: LS
authors.lastname: Ramos
authors.forename: Jonathan Hale
authors.initials: JH
authors.lastname: Zippin
authors.forename: Margarita
authors.initials: M
authors.lastname: Kamenetsky
authors.forename: Jochen
authors.initials: J
authors.lastname: Buck
authors.forename: Lonny R
authors.initials: LR
authors.lastname: Levin
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage*; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D007340:Insulinoma / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D005947:Glucose