Inhibition of glucose-stimulated activation of extracellular signal-regulated protein kinases 1 and 2 by epinephrine in pancreatic beta-cells.
Glucose sensing is essential for the ability of pancreatic beta-cells to produce insulin in sufficient quantities to maintain blood glucose within the normal range. Stress causes the release of adrenergic hormones that increase circulating glucose by promoting glucose production and inhibiting insulin release. We have shown that extracellular signal-regulated kinases 1 and 2 (ERK1/2) are responsive to glucose in pancreatic beta-cells and that glucose activates ERK1/2 by mechanisms independent of insulin. Here we show that glucose-induced activation of ERK1/2 is inhibited by epinephrine through the alpha2-adrenergic receptor. Epinephrine and the selective alpha2-adrenergic agonist UK14304 reduced insulin secretion and glucose-stimulated ERK1/2 activation in a pertussis toxin-sensitive manner, implicating the alpha subunit of a Gi family member. Alpha2-adrenergic agonists also reduced stimulation of ERK1/2 by glucagon-like peptide 1 and KCl, but not by phorbol ester or nerve growth factor. Our findings suggest that alpha2-adrenergic agonists act via a Gi family member on early steps in ERK1/2 activation, supporting the idea that ERK1/2 are regulated in a manner that reflects insulin demand.
Department of Pharmacology, UT Southwestern Medical Center, 6001 Forest Park Rd., Dallas, TX 75390-9041, USA.
Tara Beers
TB
Gibson
Michael C
MC
Lawrence
Craig J
CJ
Gibson
Colleen A
CA
Vanderbilt
Kathleen
K
McGlynn
Don
D
Arnette
Wei
W
Chen
Julie
J
Collins
Bashoo
B
Naziruddin
Marlon F
MF
Levy
Barbara E
BE
Ehrlich
Melanie H
MH
Cobb
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D037342:Pertussis Toxin / Q000494:pharmacology; D051381:Rats
D000242:Cyclic AMP; D037342:Pertussis Toxin; D048052:Mitogen-Activated Protein Kinase 3; D005947:Glucose; D004837:Epinephrine