Glucose and GLP-1 stimulate cAMP production via distinct adenylyl cyclases in INS-1E insulinoma cells Academic Article uri icon


MeSH Major

  • Adenylyl Cyclases
  • Cyclic AMP
  • Glucagon-Like Peptide 1
  • Glucose
  • Insulinoma
  • Signal Transduction


  • 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.

publication date

  • September 2008



  • Academic Article



  • eng

PubMed Central ID

  • PMC2518727

Digital Object Identifier (DOI)

  • 10.1085/jgp.200810044

PubMed ID

  • 18695009

Additional Document Info

start page

  • 329

end page

  • 38


  • 132


  • 3