Change in Insulin Sensitivity or Responsiveness Is Not a Major Component of the Mechanism of Action of Ractopamine in Beef Steers123

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Abstract

Our objective was to determine whether the β-adrenergic agonist ractopamine altered sensitivity or responsiveness to insulin. We used the hyperinsulinemic, euglycemic clamp approach in five multicatheterized beef steers to evaluate insulin sensitivity (ED50) and responsiveness (Rmax or Rmin) during control or ractopamine feeding (80 mg/kg feed). Steers had blood vessel catheters and ultrasound flow probes that allowed measurement of net uptake and release of glucose and insulin by portal-drained viscera (PDV), liver and hindlimb. Steers ate meals of equal size every 2 h. Steers were fed at 1.8 times calculated maintenance energy. The design was a single reversal. Two rates of insulin infusion followed a base-line period on each of three sample days. Insulin was infused into a mesenteric vein at 10, 20, 40, 80, 160 and 320 mU/(h⋅kg body weight). During the base-line period, arterial concentrations of glucose, oxygen, nonesterified fatty acids and insulin were not different between control and ractopamine feeding. Arterial urea was lower during ractopamine than during control feeding (5.02 vs. 6.20 mmol/L, respectively, P < 0.01). Net release of glucose by liver and net uptake of glucose by the hindlimb were not affected by treatment. Similarly, net release of insulin by PDV and net uptake of insulin by liver were not affected by treatment. The Rmax and ED50 for steady-state glucose infusion rate, total glucose entry, hepatic glucose production and hindlimb glucose uptake did not differ between treatments. There was a trend for a lower ED50 in hindlimb with ractopamine treatment (P < 0.13). These data do not support a change in sensitivity or responsiveness of tissues to insulin as a major component of the mechanism of action of ractopamine.

β-adrenergic agonist
ractopamine
insulin
glucose metabolism
cattle

Abbreviations used:

BW
body weight
ED50
the insulin concentration required for 50% maximal response
MCR
metabolic clearance rate
NEFA
nonesterified fatty acids
PAH
p-aminohippurate
PDV
portal-drained viscera
Rmax
the maximal response to insulin
SSGIR
steady-state glucose infusion rate
TGE
total glucose entry

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1

Presented in part at the annual meeting of the American Institute of Nutrition, April, 1994, Anaheim, CA [Eisemann, J. H. & Bristol, D. G. (1994) Insulin sensitivity and responsiveness in steers fed control or ractopamine-treated feed. FASEB J. 8: A158 (abs.)].

2

Supported in part by Eli Lilly Research Laboratories and Company, Greenfield, IN; The Institute of Nutrition of the University of North Carolina, Chapel Hill, NC and by the North Carolina ARS. Ractopamine and insulin for the study were both donated by D. B. Anderson, Lilly Research Laboratories. The use of trade names in this publication does not imply endorsement by the North Carolina ARS nor criticism of similar products not mentioned.

3

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 USC section 1734 solely to indicate this fact.