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

Tara Beers Gibson, Michael C. Lawrence, Craig J. Gibson, Colleen A. Vanderbilt, Kathleen McGlynn, Don Arnette, Wei Chen, Julie Collins, Bashoo Naziruddin, Marlon F. Levy, Barbara E. Ehrlich, Melanie H. Cobb

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Glucose sensing is essential for the ability of pancreatic β-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 β-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 α2-adrenergic receptor. Epinephrine and the selective 2-adrenergic agonist UK14304 reduced insulin secretion and glucose-stimulated ERK1/2 activation in a pertussis toxin-sensitive manner, implicating the subunit of a Gi family member α2-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 2-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.

Original languageEnglish (US)
Pages (from-to)1066-1073
Number of pages8
JournalDiabetes
Volume55
Issue number4
DOIs
StatePublished - Jul 27 2006

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Gibson, T. B., Lawrence, M. C., Gibson, C. J., Vanderbilt, C. A., McGlynn, K., Arnette, D., Chen, W., Collins, J., Naziruddin, B., Levy, M. F., Ehrlich, B. E., & Cobb, M. H. (2006). Inhibition of glucose-stimulated activation of extracellular signal-regulated protein kinases 1 and 2 by epinephrine in pancreatic β-cells. Diabetes, 55(4), 1066-1073. https://doi.org/10.2337/diabetes.55.04.06.db05-1266