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β-Adrenergic Responsive Induction of Insulin Resistance in Liver of Aging Rats.
MedLine Citation:
PMID:  21438725     Owner:  NLM     Status:  Publisher    
Introduction. We previously demonstrated increases in β-adrenergic receptor (β-AR) density in rat liver, in association with increased β-AR-mediated stimulation of glucose output in rat hepatocytes, during senescent aging. We therefore hypothesized that pharmacologic β-adrenergic stimulation might induce insulin resistance and glucose output in liver of aging rats in vivo. Methods. In this study, pancreatic clamps were performed on young adult (4-month-old) and senescent (24-month-old) Fischer 344 male rats by infusing somatostatin (3 μg/kg/min) at time 0 to inhibit insulin secretion, and then infusing insulin (1 mU/kg/min) to replace basal insulin concentrations. At time 0 rats also received either the β-AR agonist isoproterenol (100 ng/kg/min) or saline (control). After 120 min the insulin infusion rate was increased to 4 mU/kg/min for an additional 120 min. Tritiated glucose was infused throughout the study to measure glucose turnover rates. Results and Conclusion. The results of the pancreatic clamp studies demonstrated that under saline control conditions hepatic glucose production (HGP) was suppressed during hyperinsulinemia in both young and old rats, with a trend toward reduced insulin sensitivity in the older animals. Isoproterenol infusion impaired insulin-induced suppression of HGP in both age groups. The results suggest that β-AR stimulation by isoproterenol increases HGP and acutely induces hepatic insulin resistance in both young and old rats. A similar role for β-adrenergic-mediated hepatic insulin resistance in aging humans would suggest a novel therapeutic target for the treatment or prevention of glucose dysregulation and diabetes developing with advancing age.
Giovanna Muscogiuri; Amrita Kamat; Bogdan Balas; Andrea Giaccari; Ralph A Defronzo; Nicolas Musi; Michael S Katz
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-26
Journal Detail:
Title:  Endocrine research     Volume:  -     ISSN:  1532-4206     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8408548     Medline TA:  Endocr Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
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