Inhibition of glucose-stimulated activation of extracellular signal-regulated protein kinases 1 and 2 by epinephrine in pancreatic beta-cells.

Abstract:

: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.

journal_name

Diabetes

journal_title

Diabetes

authors

Gibson TB,Lawrence MC,Gibson CJ,Vanderbilt CA,McGlynn K,Arnette D,Chen W,Collins J,Naziruddin B,Levy MF,Ehrlich BE,Cobb MH

doi

10.2337/diabetes.55.04.06.db05-1266

subject

Has Abstract

pub_date

2006-04-01 00:00:00

pages

1066-73

issue

4

eissn

0012-1797

issn

1939-327X

pii

55/4/1066

journal_volume

55

pub_type

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