Skip to main content
Download PDF
  • Published:

Clenbuterol-Induced Insulin Resistance in Calves Measured by Hyperinsulinemic, Euglycemic Clamp Technique

Clenbuterolinducerad insulinresistens hos kalv studerad med hyperinsulinemisk, euglykemisk damp teknik

Acta Veterinaria Scandinavica volume 39, pages 281–289 (1998)Cite this article

Abstract

Hyperinsulinemic, euglycemic clamp tests were performed on calves before and after clenbuterol treatment. Clenbuterol was given as 2 intramuscular injections with an interval of about 12 h. The dose used was 1 μg/kg b.w. The treatment resulted in increased plasma levels of insulin and glucose. The results of the clamp tests showed that clenbuterol induced a transient decrease in insulin sensitivity. Both insulin mediated glucose disposal (M), expressed as μmol/kg live b.w./min. and the M/I-index (M divided by the average insulin concentration at steady state) were significantly reduced after treatment. The effect of clenbuterol on carbohydrate metabolism seemed to be rather short-lived, since significant changes occurred only in animals treated 5-6 h prior to the test. According to the literature, the metabolic effects of clenbuterol have been studied only after the high doses used for growth promoting purposes. The results from the present study showed that similar changes occur also after doses at the therapeutic level. The hyperinsulinemic, euglycemic clamp test was considered to be a valuable tool for the study of insulin sensitivity in cattle.

Sammanfattning

Hyperinsulinemisk, euglykemisk clamp test utfördes på kalvar före och efter behandling med clenbuterol. Två i.m. injektioner gavs med 12 timmars intervall. Den använda dosen var 1μg/kg kroppsvikt. Behandlingen resulterade i ökade plasmakoncentrationer av insulin och glykos. Resultaten av clamptesterna visade att clenbuterolbehandlingen resulterat i nedsatt insulinkänslighet. Det insulinmedierade vävnadsupptaget av glykos, M, uttryckt i μmol/kg kroppsvikt/min och insulinkänslighetsindex, M/I (M delat med medelinsulinkoncentrationen), var signifikant reducerade efter clenbuterolbehandling.

Effekten av clenbuterol var relativt kortlivad, insulinresistens påvisades endast hos de kalvar som behandlats 5–6 timmar innan testet.

Enligt tillgängliga litteraturuppgifter har tidigare effekter av clenbuterol endast studerats efter de höga doser som använts i tillväxtstimulerande syfte. Resultaten från denna studie visar att samma effekter kan induceras av terapeutiska doser.

References

  • Alzaid A, Rizza RA: Insulin resistance and its role in the pathogenesis of impaired glucose tolerance and non-insulin-dependent diabetes mellitus: Perspectives gained from in vivo studies. In Insulin resistance. Ed. Moller DE, John Wiley & Sons, Chichester, New York, Brisbane, Toronto, Singapore 1993.

    Google Scholar 

  • Blum JW, Flückiger N: Early metabolic and endocrine effects of perorally administered ß-adreno-ceptor agonists in calves. Eur. J. Pharmacol. 1988,757, 177–187.

    Article  Google Scholar 

  • Campaigne BN, Gunnarsson R: The effects of physical training in people with insulin-dependent diabetes. Diabetic Med. 1988, 5, 429–433.

    Article  CAS  Google Scholar 

  • Debuf Y(ed): The Veterinary Formularly. The Pharmaceutical Press, London 1991.

    Google Scholar 

  • DeFronzo RA, Tobin JD, Andres R: Glucose clamp technique: A method for quantifying insulin secretion and resistance. Amer. J. Physiol. 1979, 237, 214–233.

    Google Scholar 

  • Hay WW, Sparks JW, Gilbert M, Battaglia FC, Mes-chia G: Effect of insulin on glucose uptake by the maternal hindlimb and uterus, and by the fetus in conscious pregnant sheep. J. Endocrinol. 1984, 100, 119–124.

    Article  CAS  Google Scholar 

  • Hart IC, Bines JA, Morant SV, Ridley JL: Endocrine control of energy metabolism in the cow: Comparison of the levels of hormones (prolactin, growth hormone, insulin and thyroxine) and metabolites in the plasma of the high- and low-yielding cattle at various stages of lactation. J. Endocrinol. 1978, 77, 333–345.

    Article  CAS  Google Scholar 

  • Heinemann L, Heise T, Ampudia J, Sawicki P, Sin-delka G, Brunner G, Starke AR: Four week administration of an ACE inhibitor and a cardiose-lective ß-blocker in healthy volunteers: no influence on insulin sensitivity. Eur. J. Clin. Inv. 1995, 25, 595–600.

    Article  CAS  Google Scholar 

  • Herbein JH, Aiello RJ, Eckler LI, Pearson RE, Akers RM: Glucagon, insulin, growth hormone, and glucose concentrations in blood plasma of lactating dairy cows. J. Dairy Sci. 1985, 68, 320–325.

    Article  CAS  Google Scholar 

  • Hostettler-Allen RL, Tappy L, Blum JW: Insulin resistance, hyperglycemia, and glucosuria in intensively milk fed calves. J. Anim. Sci. 1994, 72, 160–173.

    Article  CAS  Google Scholar 

  • Hove K: Maintenance of lactose secretion during acute insulin deficiency in lactating goats. Acta Physiol. Scand. 1978,103, 173–179.

    Article  CAS  Google Scholar 

  • Hove K, Haise K: Abscence of feeding - induced variations in plasma insulin in hypoglycaemic -ketonemic cows. Acta Vet. Scand. 1978,79, 215–228.

    Google Scholar 

  • Hanni A, Berglund L, Reneland R, Andersson PE, Lindh L, Lithell H: The alterations in insulin sensitivity during angiotensin converting enzyme inhibitor treatment are related to the calcium/magnesium balance. Am. J. Hypertens. 1997, 10, 145–151.

    Article  Google Scholar 

  • Kirsch M, Baumgarten M, Deufel T, Rinninger F, Kemmler W, Häring U: Catecholamine-induced insulin resistance of glucose transport in isolated rat adipocytes. Biochem.J. 1983,216, 737–745.

    Article  CAS  Google Scholar 

  • Lindsay DB, Hunter RA, Sillence MN: The use of non-peptide hormones and analogues to manipulate animal performance. In The control of fat and lean disposition. Ed. Buttery PJ, Boormann KN, Lindsay DB. Butterworth-Heinemann, Oxford 1992.

    Google Scholar 

  • Luthman J, Jacobsson SO: Acute metabolic effects of clenbuterol in calves. Acta vet.scand. 1993, 34, 169–174.

    CAS  PubMed  Google Scholar 

  • Luthman J, Holtenius P: Norepinephrine-induced hypocalcemia and fatty liver in sheep. Acta vet.-scand. 1972, 73,31–38

    Google Scholar 

  • Metcalf JA, Weekes TEC: Effect of plane of nutrition on insulin sensitivity during lactation in the ewe. J. Dairy Res. 1990, 57, 465–478.

    Article  CAS  Google Scholar 

  • Pessin JE, Gitomer W, Oka Y, Oppenheimer CL, Czech MP: Adrenergic regulation of insulin and epidermal growth factor in rat adipocytes. J. Biol. Chem. 1983, 258, 7386–7394.

    CAS  PubMed  Google Scholar 

  • Pollare T, Lithell H, Berne C: Insulin resistance is a characteristic feature of primary hypertension independent of obesity. Metabolism 1990,39, 167–174

    Article  CAS  Google Scholar 

  • Sano H, Nakai M, Kondo T, Terashima Y: Insulin responsiveness to glucose and tissue responsiveness to insulin in lactating pregnant, and nonpregnant, non.lactating beef cows. J. Anim. Sci. 1991,69, 1122–1127.

    Article  CAS  Google Scholar 

  • Sano H, Narahara S, Kondo T, Takahashi A, Terashima Y: Insulin responsiveness to glucose and tissue responsiveness to insulin during lactation in dairy cows. Dom. Anim. Endocrinol. 1993, 10, 191–197.

    Article  CAS  Google Scholar 

  • Sartin JL, Kemppainen RJ, Cummins KA, Williams JC: Plasma concentrations of metabolic hormones in high and low producing dairy cows. J. Dairy Sci. 1988, 71, 650–657.

    Article  CAS  Google Scholar 

  • Tappy L, Randin D, Vollenweider L, Paquot N, Scherrer U, Schneiter P, Nicod P, Jéquier E: Mechanisms of dexamethasoneinduced insulin resistance in healthy humans. J. Clin. Endocrinol. Metab. 1994, 79, 1063–1069.

    CAS  PubMed  Google Scholar 

  • Vasilatos R, Wangsness PJ: Diurnal variation in plasma insulin and growth hormone associated with two stages of lactation in high producing dairy cows. Endocrinnology 1981,108, 300–304.

    Article  CAS  Google Scholar 

  • Wallberg-Henriksson H, Wahren A: Effects of nutrition and diabetes mellitus on the regulation of metabolic fuels during exercise. Amer. J. Clin. Nutr. 1989, 49, 938–943.

    Article  CAS  Google Scholar 

  • Zimmerli V, Blum JV: Acute and long-term metabolic, endocrine, respiratory, cardiac and skeletal muscle activity changes in response to perorally administered ß-adrenoeeptor agonists in calves. J. Anim. Physiol. Anim. Nutr. 1990, 63, 157–172.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ruminant Medicine and Veterinary Epidemiology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, P.O. Box 7019, S-750 07, Uppsala, Sweden

    K. Sternbauer, J. Luthman & SO. Jacobsson

  2. Department of Geriatrics, Faculty of Medicine, Uppsala University, Sweden

    A. Hänni

Authors
  1. K. Sternbauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Luthman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Hänni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. SO. Jacobsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. Sternbauer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sternbauer, K., Luthman, J., Hänni, A. et al. Clenbuterol-Induced Insulin Resistance in Calves Measured by Hyperinsulinemic, Euglycemic Clamp Technique. Acta Vet Scand 39, 281–289 (1998). https://doi.org/10.1186/BF03547800

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1186/BF03547800

Keywords

Acta Veterinaria Scandinavica

ISSN: 1751-0147