Proteomic exploration of pancreatic islets in mice null for the alpha2A adrenergic receptor.

Hu X, Friedman D, Hill S, Caprioli R, Nicholson W, Powers AC, Hunter L, Limbird LE
J Mol Endocrinol. 2005 35 (1): 73-88

PMID: 16087723 · DOI:10.1677/jme.1.01764

The present studies extend recent findings that mice null for the alpha(2A) adrenergic receptor (alpha(2A) AR KO mice) lack suppression of exogenous secretagogue-stimulated insulin secretion in response to alpha(2) AR agonists by evaluating the endogenous secretagogue, glucose, ex vivo, and providing in vivo data that baseline insulin levels are elevated and baseline glucose levels are decreased in alpha(2A) AR KO mice. These latter findings reveal that the alpha(2A) AR subtype regulates glucose-stimulated insulin release in response to endogenous catecholamines in vivo. The changes in alpha(2A) AR responsiveness and resultant changes in insulin/glucose homeostasis encouraged us to utilize proteomics strategies to identify possible alpha(2A) AR downstream signaling molecules or other resultant changes due to perturbation of alpha(2A) AR expression. Although agonist stimulation of islets from wild type (WT) mice did not significantly alter islet protein profiles, several proteins were enriched in islets from alpha(2A) AR KO mice when compared with those from WT mice, including an enzyme participating in insulin protein processing. The present studies document the important role of the alpha(2A) AR subtype in tonic suppression of insulin release in response to endogenous catecholamines as well as exogenous alpha(2) agonists and provide insights into pleiotropic changes that result from loss of alpha(2A) AR expression and tonic suppression of insulin release.

MeSH Terms (25)

Adrenergic alpha-2 Receptor Agonists Adrenergic alpha-Agonists Amino Acid Sequence Animals Base Sequence Blood Glucose Brimonidine Tartrate DNA Female Glucose Insulin Insulin Secretion In Vitro Techniques Islets of Langerhans Mice Mice, Inbred C57BL Mice, Knockout Molecular Sequence Data Protein Processing, Post-Translational Proteins Proteomics Quinoxalines Receptors, Adrenergic, alpha-2 Sequence Homology, Nucleic Acid Signal Transduction

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