Age-Related Impairment in Insulin Release The Essential Role of β<subscript>2</subscript>-Adrenergic Receptor.
In: Diabetes, Jg. 61 (2012-03-01), Heft 3, S. 692-701
academicJournal
Zugriff:
In this study, we investigated the significance of β2-adrenergic receptor (β2AR) in age-related impaired insulin secretion and glucose homeostasis. We characterized the metabolic phenotype of β2AR-null C57B1/6N mice (β2AR-/-) by performing in vivo and ex vivo experiments. In vitro assays in cultured INS-1E β-cells were carried out in order to clarify the mechanism by which β2AR deficiency affects glucose metabolism. Adult β2AR-/- mice featured glucose intolerance, and pancreatic islets isolated from these animals displayed impaired glucose-induced insulin release, accompanied by reduced expression of peroxisome proliferator-activated receptor (PPAR)γ pancreatic duodenal homeobox-1 (PDX-1), and GLUT2. Adenovirus-mediated gene transfer of human β2AR rescued these defects. Consistent effects were evoked in vitro both upon β2AR knockdown and pharmacologic treatment. Interestingly, with aging, wild-type (β2AR+/+) littermates developed impaired insulin secretion and glucose tolerance. Moreover, islets from 20-month-old β2AR+/+ mice exhibited reduced density of β2AR compared with those from younger animals, paralleled by decreased levels of PPARγ, PDX-1, and GLUT2. Overexpression of β2AR in aged mice rescued glucose intolerance and insulin release both in vivo and ex vivo, restoring PPARγ/PDX-1/GLUT2 levels. Our data indicate that reduced β2AR expression contributes to the age-related decline of glucose tolerance in mice. [ABSTRACT FROM AUTHOR]
Titel: |
Age-Related Impairment in Insulin Release The Essential Role of β<subscript>2</subscript>-Adrenergic Receptor.
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Autor/in / Beteiligte Person: | Santulli, Gaetano ; Lombardi, Angela ; Sorriento, Daniela ; Anastasio, Antonio ; Del Giudice, Carmine ; Formisano, Pietro ; Béguinot, Francesco ; Trimarco, Bruno ; Miele, Claudia ; Iaccarino, Guido |
Zeitschrift: | Diabetes, Jg. 61 (2012-03-01), Heft 3, S. 692-701 |
Veröffentlichung: | 2012 |
Medientyp: | academicJournal |
ISSN: | 0012-1797 (print) |
DOI: | 10.2337/db11-1027 |
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