Skip to main content

Advertisement

SpringerLink
Log in

Associations of ceruloplasmin and haptoglobin with inflammation and glucose in bottlenose dolphins (Tursiops truncatus)

  • Original Article
  • Published:
Comparative Clinical Pathology Aims and scope Submit manuscript

Abstract

Bottlenose dolphins (Tursiops truncatus) have a diabetes-like metabolism and are susceptible to conditions, including chronic inflammation, hyperglycemia, and dyslipidemia, that are associated with insulin resistance and metabolic syndrome in humans. Serum ceruloplasmin and haptoglobin levels were assessed among 58 dolphins as indicators of inflammation as well as predictors of glucose and lipids, using stepwise regression models that included age, sex, fasting status, reason for blood draw, hematocrit, white blood cell count, erythrocyte sedimentation rate (ESR), serum glucose, triglycerides, and cholesterol. The mean ± SD of ceruloplasmin and haptoglobin levels were 23 ± 8 and 32 ± 29 mg/dl, respectively. Increasing ceruloplasmin was mildly associated with increasing ESR (P = 0.001, R 2 = 0.19). The best predictors of haptoglobin levels were serum glucose and reason for blood draw; the strongest positive association between haptoglobin and glucose was among blood samples that were taken as part of an initial clinical workup (R 2 = 0.78), followed by blood samples that were taken for routine health purposes (R 2 = 0.47). This study supports that ceruloplasmin is associated with ESR, a common biomarker of inflammation among dolphins, and that increasing haptoglobin is associated with increasing glucose.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Alsemgeest SPM, Kalsbeek HC, Wensing T, Koeman JP, Van Ederen AM, Gruys E (1994) Concentrations of serum amyloid-A (SAA) and haptoglobin (HP) as parameters of inflammatory diseases in cattle. Vet Q 16:21–23

    Article  CAS  PubMed  Google Scholar 

  • Bergstrand CG, Furst P, Larsson Y, Sterky G (1962) Serum haptoglobin in juvenile diabetes. Scand J Clin Lab Invest 14:629–632

    Article  CAS  PubMed  Google Scholar 

  • Chacko SK, Cheluvappa R (2010) Increased ceruloplasmin and fibrinogen in type 2 diabetes corresponds to decreased anti-oxidant activity in a preliminary tertiary South Indian hospital study. Exp Clin Endocrinol Diabetes 118:64–67

    Article  CAS  PubMed  Google Scholar 

  • Chiellini C, Santini F, Marsili A, Berti P, Bertacca A, Pelosini C, Scartabelli G, Pardini E, Lopez-Soriano J, Centoni R, Ciccarone AM, Benzi L, Vitti P, Del Prato S, Pinchera A, Maffei M (2004) Serum haptoglobin: a novel marker of adiposity in humans. J Clin Endocrinol Metab 89:2678–2683

    Article  CAS  PubMed  Google Scholar 

  • Conway BR, Savage DA, Brady HR, Maxwell AP (2007) Association between haptoglobin gene variants and diabetic nephropathy: haptoglobin polymorphism in nephropathy susceptibility. Nephron Exp Nephrol 105:e75–e79

    Article  CAS  PubMed  Google Scholar 

  • Cunningham J, Leffell M, Mearkle P, Harmatz P (1995) Elevated plasma ceruloplasmin in insulin-dependent diabetes mellitus: evidence for increased oxidative stress as a variable complication. Metab Clin Exp 44:996–999

    Article  CAS  PubMed  Google Scholar 

  • Daimon M, Susa S, Yamatani K, Manaka H, Hama K, Kimura M, Ohnuma H, Kato T (1998) Hyperglycemia is a factor for an increase in serum ceruloplasmin in type 2 diabetes. Diabetes Care 21:1525–1528

    Article  CAS  PubMed  Google Scholar 

  • Delanghe JR, Langlois MR (2002) Haptoglobin polymorphism and body iron stores. Clin Chem Lab Med 40:212–216

    Article  CAS  PubMed  Google Scholar 

  • Demetriou JA, Drewes PA, Gin JB (1974) Ceruloplasmin. In: Henry RJ, Cannon DC, Winkelman JW (eds) Clinical chemistry: principles and techniques. Harper and Row, New York, pp 857–886

    Google Scholar 

  • Fenwick BW, Schroeder JP (1988) Acute phase response kinetics of the dolphin: Diagnosis and therapeutic considerations. Abstracts presented at the International Association for Aquatic Animal Medicine 20th Annual Meeting, Kailua, Hawaii. 20:84

  • Fox PL, Mukhopadhyay C, Ehrenwald E (1995) Structure, oxidant activity, and cardiovascular mechanisms of human ceruloplasmin. Life Sci 56:1749–1758

    Article  CAS  PubMed  Google Scholar 

  • Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C (2004) Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 109:433–438

    Article  PubMed  Google Scholar 

  • Hall WF, Eurell TE, Hansen RD, Herr LG (1992) Serum haptoglobin concentration in swine naturally or experimentally infected with Actinobacillus pleuropneumoniae. J Am Vet Med Assoc 201:1730–1733

    CAS  PubMed  Google Scholar 

  • Halliwell B, Gutteridge JM (1990) The antioxidants of human extracellular fluids. Arch Biochem Biophys 280:1–8

    Article  CAS  PubMed  Google Scholar 

  • Heegaard PMH, Godson DL, Toussaint MJM, Tjornehoj K, Larsen LE, Viuff B, Ronsholt L (2000) The acute phase response of haptoglobin and serum amyloid A (SAA) in cattle undergoing experimental infection with bovine respiratory syncytial virus. Vet Immunol Immunopathol 77:151–159

    Article  CAS  PubMed  Google Scholar 

  • Johnson SP, Venn-Watson S, Cassle SE, Smith CR, Jensen ED, Ridgway SH (2009) Use of phlebotomy treatment in Atlantic bottlenose dolphins with iron overload. J Am Vet Med Assoc 235:194–200

    Article  CAS  PubMed  Google Scholar 

  • Kim CH, Park JY, Kim JY, Choi CS, Kim YI, Chung YE, Lee MS, Hong SK, Lee KU (2002) Elevated serum ceruloplasmin levels in subjects with metabolic syndrome: a population-based study. Metab Clin Exp 51:838–842

    Article  CAS  PubMed  Google Scholar 

  • Levy AP, Purushothaman R, Levy NS, Purushothaman M, Strauss M, Asleh R, Marsh S, Cohen O, Moestrup SK, Moller HJ, Zias EA, Benhayon D, Fuster V, Moreno PR (2007) Downregulation of the hemoglobin scavenger receptor in individuals with diabetes and the Hp 2-2 genotype: implications for the response to intraplaque hemorrhage and plaque vulnerability. Circ Res 101:106–110

    Article  CAS  PubMed  Google Scholar 

  • Marchand A, Galen RS, Van Lente F (1980) The predictive value of serum haptoglobin in hemolytic disease. JAMA 243:1909–1911

    Article  CAS  PubMed  Google Scholar 

  • Margerison ACF, Mann JR (1985) Serum copper, serum ceruloplasmin, and erythrocyte sedimentation rate measurements in children with Hodgkin's disease, non-Hodgkin's lymphoma, and nonmalignant lymphadenopathy. Cancer 55:1501–1506

    Article  CAS  PubMed  Google Scholar 

  • Mazzaro LM, Johnson SP, Fair PA, Bossart G, Carlin KP, Jensen ED, Smith CR, Andrews GA, Chavey PS, Venn-Watson S (2012) Iron indices among bottlenose dolphins (Tursiops truncatus): identifying populations at risk for iron overload. Comp Med 62:508–515

    Google Scholar 

  • McMillan DE (1989) Increased levels of acute-phase serum proteins in diabetes. Metab Clin Exp 38:1042–1046

    Article  CAS  PubMed  Google Scholar 

  • Medway W, Geraci JR (1986) Clinical pathology of marine mammals. In: Fowler ME (ed) Zoo and wild animal medicine, 2nd edn. Saunders, Philadelphia, pp 791–797

    Google Scholar 

  • Memisogullari R, Bakan E (2004) Levels of ceruloplasmin, transferrin, and lipid peroxidation in the serum of patients with type 2 diabetes mellitus. J Diabetes Complicat 18:193–197

    Article  PubMed  Google Scholar 

  • Muscari A, Antonelli S, Bianchi G, Cavrini G, Dapporto S, Ligabue A, Ludovico C, Magalotti D, Poggiopollini G, Zoli M, on behalf of the Pianoro Study Group (2007) Serum C3 is a stronger inflammatory marker of insulin resistance than C-reactive protein, leukocyte count, and erythrocyte sedimentation rate: comparison study in an elderly population. Diabetes Care 30:2362–2368

    Article  CAS  PubMed  Google Scholar 

  • Nakagawa T, Muramoto Y, Hori M, Mihara S, Marubayashi T, Nakagawa K (2008) A preliminary investigation of the association between haptoglobin polymorphism, serum ferritin concentration and fatty liver disease. Clin Chim Acta 398:34–38

    Article  CAS  PubMed  Google Scholar 

  • Nyman M (1959) Serum haptoglobin: methodological and clinical studies. Scand J Clin Lab Invest 11(Suppl 39):1–169

    CAS  PubMed  Google Scholar 

  • Petersen HH, Nielsen JP, Heegaard PM (2004) Application of acute phase protein measurements in veterinary clinical chemistry. Vet Res 35:163–187

    Article  CAS  PubMed  Google Scholar 

  • Pickup JC (2004) Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 27:813–823

    Article  PubMed  Google Scholar 

  • Rice EW (1961) Evaluation of the role of ceruloplasmin as an acute-phase reactant. Clin Chim Acta 6:652–655

    Article  CAS  PubMed  Google Scholar 

  • Ridgway SH, Simpson JG, Patton GS, Gilmartin WG (1970) Hematologic findings in certain small cetaceans. J Am Vet Med Assoc 157:566–575

    CAS  PubMed  Google Scholar 

  • Smith JE, Chavey PS, Andrews GA (1998) Semiautomatic and robotic methods for determining serum haptoglobin levels. Vet Clin Pathol 27:11–14

    Article  PubMed  Google Scholar 

  • Suleiman M, Aronson D, Asleh R, Kapeliovich MR, Roguin A, Meisel SR, Shochat M, Sulieman A, Reisner SA, Markiewicz W, Hammerman H, Lotan R, Levy NS, Levy AP (2005) Haptoglobin polymorphism predicts 30-day mortality and heart failure in patients with diabetes and acute myocardial infarction. Diabetes 54:2802–2806

    Article  CAS  PubMed  Google Scholar 

  • Venn-Watson S, Ridgway SH (2007) Big brains and blood glucose: common ground for diabetes mellitus in humans and healthy dolphins. Comp Med 57:390–395

    CAS  PubMed  Google Scholar 

  • Venn-Watson S, Jensen ED, Ridgway SH (2007) Effects of age and sex on clinicopathologic reference ranges in a healthy managed Atlantic bottlenose dolphin population. J Am Vet Med Assoc 231:596–601

    Article  PubMed  Google Scholar 

  • Venn-Watson S, Smith CR, Johnson S, Daniels R, Townsend F (2010) Clinical relevance of urate nephrolithiasis in bottlenose dolphins (Tursiops truncatus). Dis Aquat Org 89:167–177

    Article  CAS  PubMed  Google Scholar 

  • Venn-Watson S, Carlin K, Ridgway S (2011a) Dolphins as animal models for type 2 diabetes: sustained, postprandial hyperglycemia and hyperinsulinemia. Gen Comp Endocrinol 170:193–199

    Article  CAS  PubMed  Google Scholar 

  • Venn-Watson S, Smith CR, Gomez F, Jensen ED (2011b) Physiology of aging among healthy, older bottlenose dolphins (Tursiops truncatus): comparisons with aging humans. J Comp Physiol B 181:667–680

    Article  PubMed  Google Scholar 

  • Venn-Watson S, Benham C, Carlin K, St. Leger (2012) Hemochromatosis and fatty change: building evidence for insulin resistance in bottlenose dolphins (Tursiops truncatus). J Zoo Wildlf Med 43:S35–S47

    Google Scholar 

Download references

Acknowledgments

The authors wish to thank the animal care staff at the Navy Marine Mammal Program for collection of samples used in this study, Dr. Sam Ridgway for his initial work with dolphin glucose metabolism, and Dr. Laura Kienker at the Office of Naval Research. This study was supported by the Office of Naval Research Award Number N000141210294. This work constitutes scientific contribution nu.218 from the Sea Research Foundation. The experiments in this study complied with current US laws.

Author information

Authors and Affiliations

  1. National Marine Mammal Foundation, 2240 Shelter Island Drive, Suite 200, San Diego, CA, 92106, USA

    Stephanie Venn-Watson & Kevin P. Carlin

  2. Kansas State Veterinary Diagnostic Laboratory, 1800 Denison Avenue, Manhattan, KS, 66506, USA

    Gordon A. Andrews & Patricia S. Chavey

  3. Mystic Aquarium, a Division of Sea Research Foundation, 55 Coogan Boulevard, Mystic, CT, 06355, USA

    Lisa Mazzaro

Authors
  1. Stephanie Venn-Watson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kevin P. Carlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gordon A. Andrews
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Patricia S. Chavey
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lisa Mazzaro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stephanie Venn-Watson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Venn-Watson, S., Carlin, K.P., Andrews, G.A. et al. Associations of ceruloplasmin and haptoglobin with inflammation and glucose in bottlenose dolphins (Tursiops truncatus). Comp Clin Pathol 23, 1031–1036 (2014). https://doi.org/10.1007/s00580-013-1738-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00580-013-1738-0

Keywords

Search

Navigation