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Journal of veterinary internal medicine2011; 25(2); 356-364; doi: 10.1111/j.1939-1676.2011.0681.x

Effects of the insulin-sensitizing drug pioglitazone and lipopolysaccharide administration on insulin sensitivity in horses.

Abstract: Obesity and insulin resistance increase the risk of laminitis in horses. Pioglitazone (PG) is an insulin-sensitizing drug used in humans that is absorbed after oral administration to horses. Objective: PG treatment will increase insulin sensitivity and transcript abundance of glucose and lipid transporters in adipose and skeletal muscle tissues. Methods: Sixteen lean, healthy horses. Methods: Eight horses were administered PG (1 mg/kg bodyweight PO) for 12 days before induction of insulin resistance through IV administration of lipopolysaccharide (LPS). Treated and untreated controls (CN; n = 8) were subjected to testing of peripheral insulin sensitivity and biopsies of both subcutaneous (nuchal ligament) adipose tissue and skeletal muscle before and after treatment, and 24 hours after LPS administration. Results: PG treatment did not improve basal insulin sensitivity (CNs: 1.4 ± 0.3, PG-treated: 1.9 ± 1.3; P > .4) or mitigate LPS-induced insulin resistance (CNs: 0.4 ± 0.3, PG-treated: 0.4 ± 0.3); however, transcript abundance of glucose and lipid transporters was altered in both skeletal muscle and subcutaneous adipose tissue. Conclusions: Either a higher dose or longer treatment period might be required for physiological effects to be observed. PG is a novel therapeutic agent requiring further investigation in horses in order to determine treatment efficacy.
Publication Date: 2011-02-11 PubMed ID: 21314724DOI: 10.1111/j.1939-1676.2011.0681.xGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research investigates the effects of the insulin-sensitizing drug pioglitazone on insulin sensitivity in horses, particularly in relation to obesity and laminitis. However, it was found that the drug did not improve basal insulin sensitivity but altered the abundance of glucose and lipid transporters in muscle and adipose tissues.

Objective and Methods

  • The objective of this study was to determine if the drug pioglitazone (PG) could increase insulin sensitivity and the abundance of glucose and lipid transporters in adipose (fat) and skeletal muscle tissues, thereby mitigating risks associated with obesity in horses.
  • The researchers conducted the study on sixteen lean, healthy horses. Eight of these horses were administered 1 mg PG per kilogram of bodyweight for 12 days. The other eight horses acted as untreated controls.
  • Following the administration of PG, insulin resistance was artificially induced in the horses through an Intravenous (IV) injection of lipopolysaccharide (LPS).
  • Both the treated and untreated horses were subjected to tests for peripheral insulin sensitivity and biopsies of subcutaneous adipose tissue (fat tissue under the skin) and skeletal muscle before and after the treatments, and 24 hours after LPS administration.

Results

  • The research did not find that PG treatment improved basal insulin sensitivity in horses or mitigated LPS-induced insulin resistance, contradicting the initial hypothesis of the study. This indicates that PG may not help in increasing insulin sensitivity in horses.
  • However, the study did find that the transcript abundance of glucose and lipid transporters was altered in both skeletal muscle and subcutaneous adipose tissues. This suggests that PG has some effect on the regulation of glucose and lipids in these tissues.

Conclusions

  • The study concluded that either a higher dose or a longer treatment duration of PG might be required for physiological effects to be observed.
  • Despite these findings, the researchers maintained that PG is a novel therapeutic agent that necessitates future investigation in horses to determine its potential treatment efficacy.

Cite This Article

APA
Suagee JK, Corl BA, Wearn JG, Crisman MV, Hulver MW, Geor RJ, McCutcheon LJ. (2011). Effects of the insulin-sensitizing drug pioglitazone and lipopolysaccharide administration on insulin sensitivity in horses. J Vet Intern Med, 25(2), 356-364. https://doi.org/10.1111/j.1939-1676.2011.0681.x

Publication

ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 25
Issue: 2
Pages: 356-364

Researcher Affiliations

Suagee, J K
  • Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
Corl, B A
    Wearn, J G
      Crisman, M V
        Hulver, M W
          Geor, R J
            McCutcheon, L J

              MeSH Terms

              • Adipose Tissue / metabolism
              • Animals
              • Blood Glucose / metabolism
              • Female
              • Horse Diseases / drug therapy
              • Horse Diseases / metabolism
              • Horses / metabolism
              • Hypoglycemic Agents / pharmacology
              • Insulin / metabolism
              • Insulin Resistance
              • Lipopolysaccharides / pharmacology
              • Muscle, Skeletal / metabolism
              • Pioglitazone
              • Random Allocation
              • Thiazolidinediones / pharmacology
              • Treatment Outcome

              Citations

              This article has been cited 6 times.
              1. Durham AE, Frank N, McGowan CM, Menzies-Gow NJ, Roelfsema E, Vervuert I, Feige K, Fey K. ECEIM consensus statement on equine metabolic syndrome. J Vet Intern Med 2019 Mar;33(2):335-349.
                doi: 10.1111/jvim.15423pubmed: 30724412google scholar: lookup
              2. Morgan R, Keen J, McGowan C. Equine metabolic syndrome. Vet Rec 2015 Aug 15;177(7):173-9.
                doi: 10.1136/vr.103226pubmed: 26273009google scholar: lookup
              3. Lacombe VA. Expression and regulation of facilitative glucose transporters in equine insulin-sensitive tissue: from physiology to pathology. ISRN Vet Sci 2014;2014:409547.
                doi: 10.1155/2014/409547pubmed: 24977043google scholar: lookup
              4. Rhoads RP, Baumgard LH, Suagee JK, Sanders SR. Nutritional interventions to alleviate the negative consequences of heat stress. Adv Nutr 2013 May 1;4(3):267-76.
                doi: 10.3945/an.112.003376pubmed: 23674792google scholar: lookup
              5. Johnson PJ, Wiedmeyer CE, LaCarrubba A, Ganjam VK, Messer NT 4th. Diabetes, insulin resistance, and metabolic syndrome in horses. J Diabetes Sci Technol 2012 May 1;6(3):534-40.
                doi: 10.1177/193229681200600307pubmed: 22768883google scholar: lookup
              6. Al-Ansari AS, Duggan V, Mulcahy G, Yin X, Brennan L, Cotter PD, Patel SH, O'Donovan CM, Crispie F, Walshe N. Faecal microbiota and serum metabolome association with equine metabolic syndrome in connemara ponies. BMC Vet Res 2025 Jul 1;21(1):411.
                doi: 10.1186/s12917-025-04853-2pubmed: 40598279google scholar: lookup