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Journal of veterinary internal medicine2019; 33(3); 1483-1492; doi: 10.1111/jvim.15480

Association of sustained supraphysiologic hyperinsulinemia and inflammatory signaling within the digital lamellae in light-breed horses.

Abstract: Hyperinsulinemia is associated with equine laminitis, and digital lamellar inflammation in equine metabolic syndrome-associated laminitis (EMSAL) is modest when compared with sepsis-associated laminitis. Objective: To characterize digital lamellar inflammation in horses in a euglycemic-hyperinsulinemic clamp (EHC) model of laminitis. Methods: Sixteen healthy adult Standardbred horses. Methods: Prospective experimental study. Horses underwent EHC or saline infusion (CON) for 48 hours or until the onset of Obel grade 1 laminitis. Horses were euthanized, and digital lamellar tissue was collected and analyzed via polymerase chain reaction (pro-inflammatory cytokine and chemokine genes-CXCL1, CXCL6, CXCL8, IL-6, MCP-1, MCP-2, IL-1β, IL11, cyclooxygenases 1 and 2, tumor necrosis factor alpha [TNF-α], E-selectin, and ICAM-1), immunoblotting (phosphorylated and total signal transducer and activator of transcription 1 [STAT1], STAT3, and p38MAPK), and immunohistochemistry (markers of leukocyte infiltration: CD163, MAC387). Results: Lamellar mRNA concentrations of IL-1β, IL-6, IL-11, COX-2, and E-selectin were increased; the concentration of COX-1 was decreased; and concentrations of CXCL1, CXCL6, MCP-1, MCP-2, IL-8, TNF-α and ICAM-1 were not significantly different in the EHC group compared to the CON group (P ≤ .003). Lamellar concentrations of phosphorylated STAT proteins (P-STAT1 [S727], P-STAT1 [Y701], P-STAT3 [S727], and P-STAT3 [Y705]) were increased in the EHC group compared to the CON group, with phosphorylated STAT3 localizing to nuclei of lamellar basal epithelial cells. There was no change in the lamellar concentration of P-p38 MAPK (T180/Y182), but the concentration of total p38 MAPK was decreased in the EHC samples. There was no evidence of notable lamellar leukocyte emigration. Conclusions: These results establish a role for lamellar inflammatory signaling under conditions associated with EMSAL.
© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
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Publication Date: 2019-03-25 PubMed ID: 30912229PubMed Central: PMC6524466DOI: 10.1111/jvim.15480Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research focuses on the link between hyperinsulinemia (a condition characterized by excess insulin levels in the blood), inflammation in hoof tissues, and equine laminitis (a painful condition in horses affecting the hoof). The researchers used a euglycemic-hyperinsulinemic clamp model in horses to study the characteristics of hoof tissue inflammation and identified specific inflammatory signaling pathways associated with this condition.

Study Design and Methods

  • The study used 16 healthy adult Standardbred horses and conduced a prospective experimental study.
  • The horses were subjected to a euglycemic-hyperinsulinemic clamp (EHC), a process used to create a state of high insulin concentration in the body, or a saline infusion over 48 hours or until the onset of Obel grade 1 laminitis, an early stage of the disease characterized by noticeable lameness.
  • Once the initial period was completed, the horses were euthanized and their hoof tissues were collected for detailed molecular analyses using polymerase chain reaction, immunoblotting and immunohistochemistry techniques.

Analytical Procedures

  • Molecular tests were conducted to study the expression levels of different pro-inflammatory cytokine and chemokine genes and elements associated with inflammatory signaling, including cyclooxygenases, tumor necrosis factor alpha, E-selectin, and ICAM-1.
  • Further to ascertain the expression levels, immunoblotting was performed to study the presence and quantities of phosphorylated STAT proteins, key regulators of many cellular processes.
  • Lastly, immunohistochemistry was performed to identify markers of leukocyte infiltration, indicating inflammation.

Results of the study

  • The EHC group displayed increased expression of certain pro-inflammatory genes (e.g., IL-1β, IL-6, IL-11, COX-2, and E-selectin), and reduced expression of the COX-1 gene, in comparison to the control group.
  • Increased levels of phosphorylated STAT proteins were observed in the EHC group, indicating an active inflammatory response.
  • No significant changes were observed in the concentration of the total p38 MAPK (another key signaling protein), but the concentrations of its phosphorylated form were found to be reduced in the EHC group.
  • There were no notable instances of leukocyte emigration, indicating lack of immune system activation at the inflammation site.

Study Conclusions

  • The study establishes an association between hyperinsulinemia, inflammatory signaling in the hoof tissues, and equine laminitis.
  • The findings highlight plausible molecular mechanisms and pathways that may contribute to the manifestation of the disease.
  • This knowledge can be instrumental in developing targeted therapeutic strategies for managing equine laminitis in future.

Cite This Article

APA
Watts MR, Hegedus OC, Eades SC, Belknap JK, Burns TA. (2019). Association of sustained supraphysiologic hyperinsulinemia and inflammatory signaling within the digital lamellae in light-breed horses. J Vet Intern Med, 33(3), 1483-1492. https://doi.org/10.1111/jvim.15480

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 33
Issue: 3
Pages: 1483-1492

Researcher Affiliations

Watts, Mauria R
  • Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio.
Hegedus, Olivia C
  • Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio.
Eades, Susan C
  • Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine and Biomedical Sciences, College Station, Texas.
Belknap, James K
  • Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio.
Burns, Teresa A
  • Department of Veterinary Clinical Sciences, The Ohio State University College of Veterinary Medicine, Columbus, Ohio.

MeSH Terms

  • Animals
  • Chemokines / genetics
  • Chemokines / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Foot Diseases / veterinary
  • Glucose Clamp Technique / veterinary
  • Hoof and Claw / metabolism
  • Hoof and Claw / pathology
  • Horse Diseases / pathology
  • Horses
  • Hyperinsulinism / veterinary
  • Inflammation / veterinary
  • Prospective Studies
  • Signal Transduction

Grant Funding

  • P30 CA016058 / NCI NIH HHS
  • 2015-67015-23368 / USDA NIFA

Conflict of Interest Statement

Authors declare no conflict of interest.

References

This article includes 51 references
  1. nAmerican Association of Equine Practitionersn. AAEP membership equine research study report. www.aaepfoundation.org. Updated 2009. Accessed March 14, 2011.
  2. Treiber KH, Kronfeld DS, Geor RJ. Insulin resistance in equids: possible role in laminitis.. J Nutr 2006 Jul;136(7 Suppl):2094S-2098S.
    pubmed: 16772509doi: 10.1093/jn/136.7.2094sgoogle scholar: lookup
  3. Carter RA, Treiber KH, Geor RJ, Douglass L, Harris PA. Prediction of incipient pasture-associated laminitis from hyperinsulinaemia, hyperleptinaemia and generalised and localised obesity in a cohort of ponies.. Equine Vet J 2009 Feb;41(2):171-8.
    pubmed: 19418747doi: 10.2746/042516408x342975google scholar: lookup
  4. Karikoski NP, Patterson-Kane JC, Singer ER, McFarlane D, McGowan CM. Lamellar pathology in horses with pituitary pars intermedia dysfunction.. Equine Vet J 2016 Jul;48(4):472-8.
    pubmed: 25869529doi: 10.1111/evj.12450google scholar: lookup
  5. Karikoski NP, McGowan CM, Singer ER, Asplin KE, Tulamo RM, Patterson-Kane JC. Pathology of Natural Cases of Equine Endocrinopathic Laminitis Associated With Hyperinsulinemia.. Vet Pathol 2015 Sep;52(5):945-56.
    pubmed: 25232034doi: 10.1177/0300985814549212google scholar: lookup
  6. Asplin KE, Sillence MN, Pollitt CC, McGowan CM. Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies.. Vet J 2007 Nov;174(3):530-5.
    pubmed: 17719811doi: 10.1016/j.tvjl.2007.07.003google scholar: lookup
  7. de Laat MA, McGowan CM, Sillence MN, Pollitt CC. Equine laminitis: induced by 48 h hyperinsulinaemia in Standardbred horses.. Equine Vet J 2010 Mar;42(2):129-35.
    pubmed: 20156248doi: 10.2746/042516409x475779google scholar: lookup
  8. Leise BS, Faleiros RR, Watts M, Johnson PJ, Black SJ, Belknap JK. Hindlimb laminar inflammatory response is similar to that present in forelimbs after carbohydrate overload in horses.. Equine Vet J 2012 Nov;44(6):633-9.
    pubmed: 22212091doi: 10.1111/j.2042-3306.2011.00531.xgoogle scholar: lookup
  9. Faleiros RR, Leise BS, Watts M, Johnson PJ, Black SJ, Belknap JK. Laminar chemokine mRNA concentrations in horses with carbohydrate overload-induced laminitis.. Vet Immunol Immunopathol 2011 Nov 15;144(1-2):45-51.
    pubmed: 21889804doi: 10.1016/j.vetimm.2011.07.005google scholar: lookup
  10. Leise BS, Faleiros RR, Watts M, Johnson PJ, Black SJ, Belknap JK. Laminar inflammatory gene expression in the carbohydrate overload model of equine laminitis.. Equine Vet J 2011 Jan;43(1):54-61.
    pubmed: 21143634doi: 10.1111/j.2042-3306.2010.00122.xgoogle scholar: lookup
  11. Belknap JK. Black walnut extract: an inflammatory model.. Vet Clin North Am Equine Pract 2010 Apr;26(1):95-101.
    pubmed: 20381738doi: 10.1016/j.cveq.2009.12.007google scholar: lookup
  12. Faleiros RR, Nuovo GJ, Flechtner AD, Belknap JK. Presence of mononuclear cells in normal and affected laminae from the black walnut extract model of laminitis.. Equine Vet J 2011 Jan;43(1):45-53.
    pubmed: 21143633doi: 10.1111/j.2042-3306.2010.00121.xgoogle scholar: lookup
  13. Leise BS, Watts M, Tanhoff E, Johnson PJ, Black SJ, Belknap JK. Laminar regulation of STAT1 and STAT3 in black walnut extract and carbohydrate overload induced models of laminitis.. J Vet Intern Med 2012 Jul-Aug;26(4):996-1004.
    pubmed: 22805114doi: 10.1111/j.1939-1676.2012.00944.xgoogle scholar: lookup
  14. Pollitt CC, Visser MB. Carbohydrate alimentary overload laminitis.. Vet Clin North Am Equine Pract 2010 Apr;26(1):65-78.
    pubmed: 20381736doi: 10.1016/j.cveq.2010.01.006google scholar: lookup
  15. Faleiros RR, Johnson PJ, Nuovo GJ, Messer NT, Black SJ, Belknap JK. Laminar leukocyte accumulation in horses with carbohydrate overload-induced laminitis.. J Vet Intern Med 2011 Jan-Feb;25(1):107-15.
    pubmed: 21143304doi: 10.1111/j.1939-1676.2010.0650.xgoogle scholar: lookup
  16. Faleiros RR, Nuovo GJ, Belknap JK. Calprotectin in myeloid and epithelial cells of laminae from horses with black walnut extract-induced laminitis.. J Vet Intern Med 2009 Jan-Feb;23(1):174-81.
    pubmed: 19175737doi: 10.1111/j.1939-1676.2008.0241.xgoogle scholar: lookup
  17. de Laat MA, Clement CK, McGowan CM, Sillence MN, Pollitt CC, Lacombe VA. Toll-like receptor and pro-inflammatory cytokine expression during prolonged hyperinsulinaemia in horses: implications for laminitis.. Vet Immunol Immunopathol 2014 Jan 15;157(1-2):78-86.
    pubmed: 24246153doi: 10.1016/j.vetimm.2013.10.010google scholar: lookup
  18. Burns TA, Watts MR, Weber PS, McCutcheon LJ, Geor RJ, Belknap JK. Laminar inflammatory events in lean and obese ponies subjected to high carbohydrate feeding: Implications for pasture-associated laminitis.. Equine Vet J 2015 Jul;47(4):489-93.
    pubmed: 24963607doi: 10.1111/evj.12314google scholar: lookup
  19. Lane HE, Burns TA, Hegedus OC, Watts MR, Weber PS, Woltman KA, Geor RJ, McCutcheon LJ, Eades SC, Mathes LE, Belknap JK. Lamellar events related to insulin-like growth factor-1 receptor signalling in two models relevant to endocrinopathic laminitis.. Equine Vet J 2017 Sep;49(5):643-654.
    pubmed: 28078757doi: 10.1111/evj.12663google scholar: lookup
  20. Henneke DR, Potter GD, Kreider JL, Yeates BF. Relationship between condition score, physical measurements and body fat percentage in mares.. Equine Vet J 1983 Oct;15(4):371-2.
    pubmed: 6641685doi: 10.1111/j.2042-3306.1983.tb01826.xgoogle scholar: lookup
  21. Menzies-Gow NJ, Stevens KB, Sepulveda MF, Jarvis N, Marr CM. Repeatability and reproducibility of the Obel grading system for equine laminitis.. Vet Rec 2010 Jul 10;167(2):52-5.
    pubmed: 20622203doi: 10.1136/vr.c3668google scholar: lookup
  22. Obel N. Studies on the Histopathology of Acute Laminitis. Uppsala, Sweden: Almqvist & Wiksell Boktryckeri; 1948.
  23. Godman JD, Burns TA, Kelly CS, Watts MR, Leise BS, Schroeder EL, van Eps AW, Belknap JK. The effect of hypothermia on influx of leukocytes in the digital lamellae of horses with oligofructose-induced laminitis.. Vet Immunol Immunopathol 2016 Oct 1;178:22-8.
    pubmed: 27496739doi: 10.1016/j.vetimm.2016.05.013google scholar: lookup
  24. Li H, Lee J, He C, Zou MH, Xie Z. Suppression of the mTORC1/STAT3/Notch1 pathway by activated AMPK prevents hepatic insulin resistance induced by excess amino acids.. Am J Physiol Endocrinol Metab 2014 Jan 15;306(2):E197-209.
    pmc: PMC3920006pubmed: 24302004doi: 10.1152/ajpendo.00202.2013google scholar: lookup
  25. Tang T, Zhang J, Yin J, Staszkiewicz J, Gawronska-Kozak B, Jung DY, Ko HJ, Ong H, Kim JK, Mynatt R, Martin RJ, Keenan M, Gao Z, Ye J. Uncoupling of inflammation and insulin resistance by NF-kappaB in transgenic mice through elevated energy expenditure.. J Biol Chem 2010 Feb 12;285(7):4637-44.
    pmc: PMC2836069pubmed: 20018865doi: 10.1074/jbc.m109.068007google scholar: lookup
  26. Lihn AS, Pedersen SB, Lund S, Richelsen B. The anti-diabetic AMPK activator AICAR reduces IL-6 and IL-8 in human adipose tissue and skeletal muscle cells.. Mol Cell Endocrinol 2008 Sep 24;292(1-2):36-41.
    pubmed: 18606210doi: 10.1016/j.mce.2008.06.004google scholar: lookup
  27. Stofkova A. Leptin and adiponectin: from energy and metabolic dysbalance to inflammation and autoimmunity.. Endocr Regul 2009 Oct;43(4):157-68.
    pubmed: 19908934
  28. Burns TA, Watts MR, Weber PS, McCutcheon LJ, Geor RJ, Belknap JK. Effect of dietary nonstructural carbohydrate content on activation of 5'-adenosine monophosphate-activated protein kinase in liver, skeletal muscle, and digital laminae of lean and obese ponies.. J Vet Intern Med 2014 Jul-Aug;28(4):1280-8.
    pmc: PMC4857936pubmed: 24750267doi: 10.1111/jvim.12356google scholar: lookup
  29. de Laat MA, Clement CK, Sillence MN, McGowan CM, Pollitt CC, Lacombe VA. The impact of prolonged hyperinsulinaemia on glucose transport in equine skeletal muscle and digital lamellae.. Equine Vet J 2015 Jul;47(4):494-501.
    pubmed: 24995680doi: 10.1111/evj.12320google scholar: lookup
  30. Asplin KE, Curlewis JD, McGowan CM, Pollitt CC, Sillence MN. Glucose transport in the equine hoof.. Equine Vet J 2011 Mar;43(2):196-201.
    pubmed: 21592215doi: 10.1111/j.2042-3306.2010.00127.xgoogle scholar: lookup
  31. Hardie DG. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy.. Nat Rev Mol Cell Biol 2007 Oct;8(10):774-85.
    pubmed: 17712357doi: 10.1038/nrm2249google scholar: lookup
  32. Mounier R, Lantier L, Leclerc J, Sotiropoulos A, Foretz M, Viollet B. Antagonistic control of muscle cell size by AMPK and mTORC1.. Cell Cycle 2011 Aug 15;10(16):2640-6.
    pubmed: 21799304doi: 10.4161/cc.10.16.17102google scholar: lookup
  33. Hardie DG. Adenosine monophosphate-activated protein kinase: a central regulator of metabolism with roles in diabetes, cancer, and viral infection.. Cold Spring Harb Symp Quant Biol 2011;76:155-64.
    pubmed: 22071265doi: 10.1101/sqb.2011.76.010819google scholar: lookup
  34. Henry WS, Laszewski T, Tsang T, Beca F, Beck AH, McAllister SS, Toker A. Aspirin Suppresses Growth in PI3K-Mutant Breast Cancer by Activating AMPK and Inhibiting mTORC1 Signaling.. Cancer Res 2017 Feb 1;77(3):790-801.
    pmc: PMC5290090pubmed: 27940576doi: 10.1158/0008-5472.can-16-2400google scholar: lookup
  35. O'Neill LA, Hardie DG. Metabolism of inflammation limited by AMPK and pseudo-starvation.. Nature 2013 Jan 17;493(7432):346-55.
    pubmed: 23325217doi: 10.1038/nature11862google scholar: lookup
  36. Towler MC, Hardie DG. AMP-activated protein kinase in metabolic control and insulin signaling.. Circ Res 2007 Feb 16;100(3):328-41.
    pubmed: 17307971doi: 10.1161/01.res.0000256090.42690.05google scholar: lookup
  37. Uotani S, Abe T, Yamaguchi Y. Leptin activates AMP-activated protein kinase in hepatic cells via a JAK2-dependent pathway.. Biochem Biophys Res Commun 2006 Dec 8;351(1):171-5.
    pubmed: 17054914doi: 10.1016/j.bbrc.2006.10.015google scholar: lookup
  38. Rendle DI, Rutledge F, Hughes KJ, Heller J, Durham AE. Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses.. Equine Vet J 2013 Nov;45(6):751-4.
    pubmed: 23600690doi: 10.1111/evj.12068google scholar: lookup
  39. Durham AE. Metformin in equine metabolic syndrome: an enigma or a dead duck?. Vet J 2012 Jan;191(1):17-8.
    pubmed: 21885304doi: 10.1016/j.tvjl.2011.08.003google scholar: lookup
  40. Watts AE, Dabareiner R, Marsh C, Carter GK, Cummings KJ. A randomized, controlled trial of the effects of resveratrol administration in performance horses with lameness localized to the distal tarsal joints.. J Am Vet Med Assoc 2016 Sep 15;249(6):650-9.
    pubmed: 27585103doi: 10.2460/javma.249.6.650google scholar: lookup
  41. Durham AE, Rendle DI, Newton JE. The effect of metformin on measurements of insulin sensitivity and beta cell response in 18 horses and ponies with insulin resistance.. Equine Vet J 2008 Jul;40(5):493-500.
    pubmed: 18482898doi: 10.2746/042516408x273648google scholar: lookup
  42. Procaccini C, De Rosa V, Galgani M, Carbone F, La Rocca C, Formisano L, Matarese G. Role of adipokines signaling in the modulation of T cells function.. Front Immunol 2013 Oct 18;4:332.
    pmc: PMC3799205pubmed: 24151494doi: 10.3389/fimmu.2013.00332google scholar: lookup
  43. Tadokoro S, Ide S, Tokuyama R, Umeki H, Tatehara S, Kataoka S, Satomura K. Leptin promotes wound healing in the skin.. PLoS One 2015;10(3):e0121242.
    pmc: PMC4370705pubmed: 25799398doi: 10.1371/journal.pone.0121242google scholar: lookup
  44. Faraj M, Beauregard G, Tardif A, Loizon E, Godbout A, Cianflone K, Vidal H, Rabasa-Lhoret R. Regulation of leptin, adiponectin and acylation-stimulating protein by hyperinsulinaemia and hyperglycaemia in vivo in healthy lean young men.. Diabetes Metab 2008 Sep;34(4 Pt 1):334-42.
    pubmed: 18562232doi: 10.1016/j.diabet.2008.01.014google scholar: lookup
  45. Schmitz O, Fisker S, Orskov L, Hove KY, Nyholm B, Møller N. Effects of hyperinsulinaemia and hypoglycaemia on circulating leptin levels in healthy lean males.. Diabetes Metab 1997 Feb;23(1):80-3.
    pubmed: 9059771
  46. Schultz N, Geor RJ, Manfredi JM. Factors associated with leptin and adiponectin concentrations in a large across breed cohort of horses and ponies. J Vet Intern Med 2014;28:998.
  47. Pleasant RS, Suagee JK, Thatcher CD, Elvinger F, Geor RJ. Adiposity, plasma insulin, leptin, lipids, and oxidative stress in mature light breed horses.. J Vet Intern Med 2013 May-Jun;27(3):576-82.
    pubmed: 23517373doi: 10.1111/jvim.12056google scholar: lookup
  48. Bamford NJ, Potter SJ, Harris PA, Bailey SR. Effect of increased adiposity on insulin sensitivity and adipokine concentrations in horses and ponies fed a high fat diet, with or without a once daily high glycaemic meal.. Equine Vet J 2016 May;48(3):368-73.
    pubmed: 25726948doi: 10.1111/evj.12434google scholar: lookup
  49. Cuadrado A, Nebreda AR. Mechanisms and functions of p38 MAPK signalling.. Biochem J 2010 Aug 1;429(3):403-17.
    pubmed: 20626350doi: 10.1042/bj20100323google scholar: lookup
  50. Leise BS, Yin C, Pettigrew A, Belknap JK. Proinflammatory cytokine responses of cultured equine keratinocytes to bacterial pathogen-associated molecular pattern motifs.. Equine Vet J 2010 May;42(4):294-303.
    pubmed: 20525046doi: 10.2746/042516409x478523google scholar: lookup
  51. Lee M, Lee E, Jin SH, Ahn S, Kim SO, Kim J, Choi D, Lim KM, Lee ST, Noh M. Leptin regulates the pro-inflammatory response in human epidermal keratinocytes.. Arch Dermatol Res 2018 May;310(4):351-362.
    pubmed: 29468452doi: 10.1007/s00403-018-1821-0google scholar: lookup

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