Glucose and GLP-1 stimulate cAMP production via distinct adenylyl cyclases in INS-1E insulinoma cells.
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.
Ramos
Lavoisier S
LS
Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10065, USA.
Zippin
Jonathan Hale
JH
Kamenetsky
Margarita
M
Buck
Jochen
J
Levin
Lonny R
LR
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*
D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D005947:Glucose