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Home / Equine Research Bank / J Vet Intern Med / Association of sustained supraphysiologic hyperinsulinemia a...
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.

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