Age-related impairment in insulin release: The essential role of β 2-adrenergic receptor

Gaetano Santulli, Angela Lombardi, Daniela Sorriento, Antonio Anastasio, Carmine Del Giudice, Pietro Formisano, Francesco Béguinot, Bruno Trimarco, Claudia Miele, Guido Iaccarino

Research output: Contribution to journalArticle

Abstract

In this study, we investigated the significance of β 2- adrenergic receptor (β 2AR) in age-related impaired insulin secretion and glucose homeostasis. We characterized the metabolic phenotype of β 2AR-null C57Bl/6N mice (β 2AR -/-) 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 β 2AR deficiency affects glucose metabolism. Adult β 2AR -/- 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 β 2AR rescued these defects. Consistent effects were evoked in vitro both upon β 2AR knockdown and pharmacologic treatment. Interestingly, with aging, wild-type (β 2AR +/+) littermates developed impaired insulin secretion and glucose tolerance. Moreover, islets from 20-month-old β 2AR +/+ mice exhibited reduced density of β 2AR compared with those from younger animals, paralleled by decreased levels of PPARγ, PDX-1, and GLUT2. Overexpression of β 2AR 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 β 2AR expression contributes to the age-related decline of glucose tolerance in mice.

Original languageEnglish
Pages (from-to)692-701
Number of pages10
JournalDiabetes
Volume61
Issue number3
DOIs
Publication statusPublished - Mar 2012

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Santulli, G., Lombardi, A., Sorriento, D., Anastasio, A., Del Giudice, C., Formisano, P., Béguinot, F., Trimarco, B., Miele, C., & Iaccarino, G. (2012). Age-related impairment in insulin release: The essential role of β 2-adrenergic receptor. Diabetes, 61(3), 692-701. https://doi.org/10.2337/db11-1027