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Domestic animal endocrinology2023; 86; 106822; doi: 10.1016/j.domaniend.2023.106822

Insulin signaling in insulin-dysregulated Icelandic horses.

Abstract: The underlying molecular mechanisms leading to insulin dysregulation are poorly understood in horses. Therefore, this study aimed to determine if insulin dysregulation is associated with an altered basal expression and extent of phosphorylation of key proteins of the insulin signaling cascade in liver (LT), muscle (MT), and subcutaneous adipose tissue (AT) under basal and stimulated conditions. Twelve Icelandic horses were subjected (1) to an oral glucose (Gluc PO) challenge and (2) to an intravenous (Ins IV) insulin challenge in a crossover study. Biopsies of LT, MT, and AT were taken in vivo under basal conditions and after Gluc PO and Ins IV stimulation. Corresponding insulin levels were measured by an equine optimized ELISA (Mercodia AB, Uppsala). Insulin levels ≥ 110 µIU/mL at 120 min indicated that six horses were insulin dysregulated (HI), while six were not (NI). Gluc PO stimulation resulted in a more pronounced hyperinsulinemia and hyperglycemia in HI horses compared to NI horses. Western blot analysis of key proteins of the insulin signaling cascade revealed an enhanced phosphorylation of the insulin receptor (InsR) under Gluc PO (P = 0.001) and Ins IV stimulation (P = 0.017) within LT, but not in MT and AT. Phosphorylation of protein kinase B was enhanced under Gluc PO stimulation in all tissues and under Ins IV stimulation in MT and AT, while phosphorylation of adenosine monophosphate protein kinase α was reduced after glucose administration (P = 0.005) in all horses. Interestingly, HI horses had significantly higher amounts of phosphorylated mechanistic target of rapamycin (mTOR) in MT (P = 0.049), irrespective of any stimulation. In LT, the amount of phosphorylated mTOR decreased under Gluc PO conditions in HI horses, while an increase was observed in NI horses (P = 0.015). A major limitation was the inclusion of only Icelandic horses of advanced age since insulin dysregulation could be related to both the equine metabolic syndrome and/or pituitary pars intermedia dysfunction. In summary, insulin signaling appeared to be maintained in both HI and NI Icelandic horses, although post-receptor alterations were observed. Thus, ID might be an equine-specific metabolic condition, in which alterations of the mTOR signaling pathway may play a crucial role, as emphasized by higher mTOR phosphorylation in HI horses.
Publication Date: 2023-10-22 PubMed ID: 39491260DOI: 10.1016/j.domaniend.2023.106822Google Scholar: Lookup
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  • Journal Article

Summary

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The research article is an investigation into the molecular mechanisms causing insulin dysregulation in Icelandic horses. The study found altered expressions and phosphorylation of proteins in key insulin signaling pathways in these horses, suggesting that insulin dysregulation may be a distinctive metabolic condition in this breed.

Research Objectives and Methodology

The researchers aimed to understand the molecular mechanisms causing insulin dysregulation in Icelandic horses. Twelve horses underwent two types of experiments: oral glucose challenge and intravenous insulin challenge. Their liver, muscle, and adipose tissue were biopsied under both challenges and under resting conditions. The research team then looked at the basal expression and phosphorylation extent of relevant proteins involved in insulin signaling in the various tissue samples collected.

Key Findings

  • Out of twelve horses, six were identified as having insulin dysregulation. These horses showed significantly higher insulin levels.
  • The glucose challenge resulted in higher insulin and glucose levels in horses with insulin dysregulation than those without it.
  • Under both challenges, enhanced phosphorylation (activation) of the insulin receptor was observed in liver tissue but not in muscle or adipose tissue.
  • Phosphorylation of a protein called protein kinase B increased in all tissues under glucose challenge and in muscle and adipose tissues under insulin challenge.
  • Phosphorylation of another protein, adenosine monophosphate protein kinase α, reduced in all horses after glucose administration.
  • All horses suffering from insulin dysregulation had higher amounts of another phosphorylated protein, the mechanistic target of rapamycin (mTOR), in their muscle tissue, regardless of stimulation.

Conclusions and Implications

The researchers concluded that although insulin signaling seems generally preserved in both insulin-dysregulated Icelandic horses and non-insulin-dysregulated ones, there were alterations observed in proteins downstream of the insulin receptor. Hence, insulin dysregulation could be considered a breed-specific metabolic condition in Icelandic horses. The increased levels of phosphorylated mTOR suggest that alterations in the mTOR signaling pathway could be a key factor in this condition.

Limitations

This study’s significant limitation is that it only incorporated older Icelandic horses. Consequently, the findings cannot be generalized to all horses since insulin dysregulation may be linked to age-related issues, such as equine metabolic syndrome or pituitary pars intermedia dysfunction.

Cite This Article

APA
Frers F, Delarocque J, Feige K, Huber K, Warnken T. (2023). Insulin signaling in insulin-dysregulated Icelandic horses. Domest Anim Endocrinol, 86, 106822. https://doi.org/10.1016/j.domaniend.2023.106822

Publication

ISSN: 1879-0054
NlmUniqueID: 8505191
Country: United States
Language: English
Volume: 86
Pages: 106822

Researcher Affiliations

Frers, F
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, Hannover 30559, Germany. Electronic address: florian.frers@tiho-hannover.de.
Delarocque, J
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, Hannover 30559, Germany.
Feige, K
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, Hannover 30559, Germany.
Huber, K
  • Institute of Animal Science, Faculty of Agricultural Sciences, University of Hohenheim, Fruwirthstr. 35, Stuttgart 70599, Germany.
Warnken, T
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, Hannover 30559, Germany; Boehringer Ingelheim Vetmedica GmbH, Binger Straße 173, Ingelheim am Rhein 55216, Germany.