Age-related impairment in insulin release: the essential role of β(2)-adrenergic receptor.

Authors:
Gaetano Santulli
Gaetano Santulli
Federico II University of Naples
Italy
Angela Lombardi
Angela Lombardi
Second University of Naples
Italy
Daniela Sorriento
Daniela Sorriento
Department of Clinical Medicine
Italy
Antonio Anastasio
Antonio Anastasio
Department of Clinical Medicine
Italy
Pietro Formisano
Pietro Formisano
Federico II University
Francesco Beguinot
Francesco Beguinot
Università di Napoli Federico II
Italy
Bruno Trimarco
Bruno Trimarco
Federico II University
Napoli | Italy

Diabetes 2012 Mar 7;61(3):692-701. Epub 2012 Feb 7.

Department of Clinical Medicine, Cardiovascular & Immunologic Sciences, Federico II University of Naples, Naples, Italy.

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

Download full-text PDF

Source
http://dx.doi.org/10.2337/db11-1027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282797PMC
March 2012
21 Reads
38 Citations
8.100 Impact Factor

Publication Analysis

Top Keywords

insulin release
12
insulin secretion
8
pdx-1 glut2
8
secretion glucose
8
impaired insulin
8
β2-adrenergic receptor
8
glucose tolerance
8
glucose intolerance
8
vivo vivo
8
β2ar
7
glucose
6
insulin
5
mice
5
defects consistent
4
rescued defects
4
human β2ar
4
consistent effects
4
β2ar rescued
4
evoked vitro
4
treatment interestingly
4

Similar Publications