β-Adrenergic responsive induction of insulin resistance in liver of aging rats

Giovanna Muscogiuri, Amrita Kamat, Bogdan Balas, Andrea Giaccari, Ralph A Defronzo, Nicolas Musi, Michael S. Katz

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)74-82
Number of pages9
JournalEndocrine Research
Volume36
Issue number2
DOIs
StatePublished - 2011

Fingerprint

Adrenergic Agents
Insulin Resistance
Glucose
Liver
Insulin
Isoproterenol
Hyperinsulinism
Somatostatin
Adrenergic Receptors
Young Adult
Hepatocytes
Age Groups
Therapeutics

Keywords

  • β-Adrenergic receptor
  • Catecholamines
  • Glucose production

ASJC Scopus subject areas

  • Endocrinology

Cite this

β-Adrenergic responsive induction of insulin resistance in liver of aging rats. / Muscogiuri, Giovanna; Kamat, Amrita; Balas, Bogdan; Giaccari, Andrea; Defronzo, Ralph A; Musi, Nicolas; Katz, Michael S.

In: Endocrine Research, Vol. 36, No. 2, 2011, p. 74-82.

Research output: Contribution to journalArticle

Muscogiuri, Giovanna ; Kamat, Amrita ; Balas, Bogdan ; Giaccari, Andrea ; Defronzo, Ralph A ; Musi, Nicolas ; Katz, Michael S. / β-Adrenergic responsive induction of insulin resistance in liver of aging rats. In: Endocrine Research. 2011 ; Vol. 36, No. 2. pp. 74-82.
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AU - Musi, Nicolas

AU - Katz, Michael S.

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