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Age-Related Impairment in Insulin Release
- Source :
- Diabetes
- Publication Year :
- 2012
- Publisher :
- American Diabetes Association, 2012.
-
Abstract
- 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 C57Bl/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.
- Subjects :
- Male
endocrine system
medicine.medical_specialty
Peroxisome proliferator-activated receptor gamma
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Peroxisome proliferator-activated receptor
Pathophysiology
Mice
Internal medicine
Internal Medicine
medicine
Animals
Insulin
Glucose homeostasis
Glucose Transporter Type 2
Homeodomain Proteins
chemistry.chemical_classification
Glucose tolerance test
biology
medicine.diagnostic_test
Pancreatic islets
Age Factors
Glucose Tolerance Test
Mice, Inbred C57BL
PPAR gamma
Phenotype
Endocrinology
medicine.anatomical_structure
chemistry
Trans-Activators
biology.protein
GLUT2
Receptors, Adrenergic, beta-2
Ex vivo
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 61
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....b1ac1a0916a9d04db976d08c4177746e