title: β-Adrenergic Responsive Induction of Insulin Resistance in Liver of Aging Rats.
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.
authors: Department of Medicine, University of Texas Health Science Center at San Antonio, Texas 78229, USA.
authors: Giovanna
authors: G
authors: Muscogiuri
authors: Amrita
authors: A
authors: Kamat
authors: Bogdan
authors: B
authors: Balas
authors: Andrea
authors: A
authors: Giaccari
authors: Ralph A
authors: RA
authors: Defronzo
authors: Nicolas
authors: N
authors: Musi
authors: Michael S
authors: MS
authors: Katz
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000375:Aging; D000818:Animals; D005947:Glucose / Q000096:biosynthesis; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology*; D013004:Somatostatin; D014316:Tritium
chemical_list: D000318:Adrenergic beta-Agonists; D007328:Insulin; D011943:Receptors, Adrenergic, beta; D014316:Tritium; D013004:Somatostatin; D005947:Glucose; D007545:Isoproterenol