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Journal of equine veterinary science2019; 82; 102797; doi: 10.1016/j.jevs.2019.102797

Pharmacodynamic Effects of Pioglitazone on High Molecular Weight Adiponectin Concentrations and Insulin Response After Oral Sugar in Equids.

Abstract: Chronic insulin dysregulation is challenging to manage with pharmaceuticals in horses. Pioglitazone improves insulin sensitivity in humans, and the pharmacokinetics of pioglitazone have been evaluated in horses. The objectives of this study were to assess the pharmacodynamic effects of oral pioglitazone on morphometric parameters, hepatic enzyme activity and function, adipokines, and enteroinsular response to oral sugar. A prospective pilot study was performed using fifteen adult equids (8 ponies, 7 horses) to evaluate the effects of short-term pioglitazone administration (2 mg/kg PO q 24 hours, 28 days). Oral sugar tests (OST) were performed before and after treatment. Adipokines were measured at day 0, 14, and 28 of administration. Plasma drug concentrations were measured at day 14 and 28 of administration. The subjects were grouped into horses, ponies, and insulin dysregulated (ID) animals. Baseline values for all parameters were compared with values obtained at day 14 and 28 using one-way or two-way analysis of variance. Mild changes were noted in morphometric parameters and hepatic enzymes. No differences were found in leptin concentrations or the blood glucose response to the OST. Significant decreases were found in the insulin response to OST at 90 and 120 minutes time points and the area under the curve after pioglitazone treatment in the pony and ID groups. High-molecular-weight (HMW) adiponectin concentrations were significantly increased in all groups after pioglitazone treatment. Decreased insulin concentrations in response to oral sugar and increased HMW adiponectin concentrations indicate positive effects of pioglitazone for treatment of metabolic derangements in equine metabolic syndrome, which warrant future clinical study.
Publication Date: 2019-09-24 PubMed ID: 31732109DOI: 10.1016/j.jevs.2019.102797Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article discusses a study that investigated the effects of pioglitazone, a drug that improves insulin sensitivity in humans, on horses and ponies. The researchers mainly evaluated its impact on insulin response after oral sugar intake.

Experiment Methodology

  • The study took the form of a prospective pilot study, with the subjects being fifteen adult equids (8 ponies, 7 horses). The researchers were investigating how the oral administration of pioglitazone (2 mg/kg PO q 24 hours, for 28 days) might affect various parameters.
  • These parameters included morphometric details, hepatic enzyme function and activity, adipokines, and an enteroinsular response to oral sugar. Hepatic enzymes refer to proteins in the liver that speed up certain chemical reactions, while adipokines are proteins that are secreted by fat cells and can influence the body’s response to insulin.
  • Oral sugar tests (OST) were carried out before and after the pioglitazone treatment, and adipokines were measured on the first day, 14th day, and the 28th day of administration. The researchers also measured plasma drug concentrations on the 14th and 28th day.
  • The animals were split into three groups: horses, ponies, and insulin dysregulated (ID) animals. The team compared the baseline values for all parameters with the values obtained on the 14th and 28th day using one-way or two-way analysis of variance.

Findings of the Study

  • The study found minor alterations in morphometric parameters and hepatic enzymes. No differences were found in leptin concentrations – leptin being a hormone that helps to regulate energy balance – or in the blood glucose response to the OST.
  • However, there was a significant decrease in the insulin response to OST at both the 90-minute and 120-minute time points and the area under the curve. This was the case after pioglitazone treatment in the pony and ID groups.
  • The concentrations of high-molecular-weight (HMW) adiponectin were significantly increased in all groups after the pioglitazone treatment. HMW adiponectin is a form of adiponectin that is larger in size and plays an important role in insulin sensitivity and glucose homeostasis.

Significance of the Research

  • The reduction in insulin response to oral sugar and the increase in HMW adiponectin concentrations suggest that pioglitazone could have positive effects if used for the treatment of metabolic issues in equine metabolic syndrome.
  • These findings highlight the need for further clinical studies on the subject. Pioglitazone, therefore, could potentially have applications in the management of insulin-related issues in equids.

Cite This Article

APA
Legere RM, Taylor DR, Davis JL, Bello K, Parker C, Judd RL, Wooldridge AA. (2019). Pharmacodynamic Effects of Pioglitazone on High Molecular Weight Adiponectin Concentrations and Insulin Response After Oral Sugar in Equids. J Equine Vet Sci, 82, 102797. https://doi.org/10.1016/j.jevs.2019.102797

Publication

ISSN: 0737-0806
NlmUniqueID: 8216840
Country: United States
Language: English
Volume: 82
Pages: 102797

Researcher Affiliations

Legere, Rebecca M
  • Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL.
Taylor, Debra R
  • Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL.
Davis, Jennifer L
  • Department of Biomedical Sciences & Pathobiology, VA-MD College of Veterinary Medicine, Blacksburg, VA.
Bello, Kaitlyn
  • Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL.
Parker, Caroline
  • Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL.
Judd, Robert L
  • Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL.
Wooldridge, Anne A
  • Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL. Electronic address: aaw0002@auburn.edu.

MeSH Terms

  • Adiponectin
  • Adult
  • Animals
  • Glucose Tolerance Test / veterinary
  • Horses
  • Humans
  • Insulin
  • Molecular Weight
  • Pilot Projects
  • Pioglitazone
  • Prospective Studies
  • Sugars
  • Veterinary Drugs