Short-term induced hyperinsulinaemia and dexamethasone challenge do not affect circulating total adiponectin concentrations in insulin-sensitive ponies.
Abstract: Hypoadiponectinaemia is a risk factor for endocrinopathic laminitis, but the directionality and nature of its association with insulin dysregulation is unclear. Objective: To investigate the effects of short-term induced hyperinsulinaemia and dexamethasone challenge on circulating [total adiponectin] and whole blood expression of adiponectin (AdipoR1 and AdipoR2), insulin, and insulin-like growth factor 1 (IGF-1) receptors in insulin-sensitive ponies. Methods: In vivo experiment. Methods: Six never-laminitic, insulin-sensitive, native-breed UK ponies first underwent a dexamethasone challenge (0.08 mg/kg i.v.) with blood samples collected every 15 min over 3 h. After a 14-day washout period, hyperinsulinaemia was induced for 9 h via a euglycaemic-hyperinsulinaemic clamp (EHC), with blood samples collected every 30 min. Serum [insulin], plasma [total adiponectin], and plasma [IGF-1] were measured using validated assays and receptor gene expression was assessed via quantitative polymerase chain reaction (qPCR). Finally, whole blood was incubated with 10-1000 ng/mL dexamethasone for 3 h at 37°C to investigate its direct effects on gene expression. Results: There were no adverse effects observed during either protocol. Dexamethasone challenge did not alter circulating [insulin] or [total adiponectin] at any time-point, but significantly upregulated AdipoR1 and IGF-1R expression at 150 and 180 min. Ex vivo incubation of whole blood with dexamethasone did not alter expression of the genes examined. There was no change in [total adiponectin] or expression of the genes examined associated with EHC-induced hyperinsulinemia. Conclusions: This was a small sample size that included only native-breed ponies; total adiponectin was measured rather than high-molecular-weight adiponectin. Conclusions: Short-term induced hyperinsulinaemia and dexamethasone challenge did not affect circulating [total adiponectin] in insulin-sensitive ponies. However, dexamethasone administration was associated with upregulation of two receptors linked to adiponectin signalling, suggesting that a physiological response occurred possibly to counteract dexamethasone-associated changes in tissue insulin sensitivity.
© 2023 MARS Horsecare and The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
Publication Date: 2023-10-06 PubMed ID: 37800859DOI: 10.1111/evj.14012Google Scholar: Lookup
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Summary
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The research explores the impact of short-term induced hyperinsulinaemia and dexamethasone challenge on insulin-sensitive ponies, particularly focusing on its effects on total adiponectin concentrations. It found no significant changes in total adiponectin levels, but a noted upregulation of two receptors associated with adiponectin signalling post dexamethasone administration.
Research Objective and Methodology
- The primary objective of this research was to examine how short-term induced hyperinsulinaemia and a dexamethasone challenge influence circulating total adiponectin concentrations and the whole blood expression of certain receptors in insulin-sensitive ponies. The focus was on adiponectin, insulin, and insulin-like growth factor 1 (IGF-1) receptors.
- For the research, six insulin-sensitive, never-laminitic, native-breed UK ponies were under experiment. Initially, these ponies underwent a dexamethasone challenge. Post a 14-day recovery period, hyperinsulinaemia was induced.
- Serum insulin, plasma total adiponectin, and plasma IGF-1 concentrations were measured using validated assays, while receptor gene expression was evaluated through quantitative polymerase chain reaction (qPCR).
- The effect of dexamethasone on gene expression was also investigated by incubating whole blood with the substance.
Research Findings
- There were no adverse effects observed during the procedure, confirming the safety of both protocols.
- The dexamethasone challenge did not cause any alteration in circulating insulin or total adiponectin levels at any measured time-point. Fluctuations were only seen in the upregulation of AdipoR1 and IGF-1R expression at 150 and 180 minutes.
- There was no impact on total adiponectin levels or the expression of the examined genes due to hyperinsulinemia induced by EHC – euglycaemic-hyperinsulinaemic clamp.
- Ex vivo dexamethasone incubation of whole blood showed no impact on the genes’ expression.
Conclusions
- Despite the small sample size and focus on native-breed ponies only, the study provided some insights about the short-term induced hyperinsulinaemia and dexamethasone challenge on insulin-sensitive ponies.
- No impact on circulating total adiponectin levels was seen. However, dexamethasone administration coincided with the upregulation of two receptor links to adiponectin signalling, suggesting a potential physiological response that could counter dexamethasone-associated changes in tissue insulin sensitivity.
Cite This Article
APA
Barnabé MA, Elliott J, Harris PA, Menzies-Gow NJ.
(2023).
Short-term induced hyperinsulinaemia and dexamethasone challenge do not affect circulating total adiponectin concentrations in insulin-sensitive ponies.
Equine Vet J.
https://doi.org/10.1111/evj.14012 Publication
Researcher Affiliations
- Department of Clinical Sciences and Services, Royal Veterinary College, Hertfordshire, UK.
- Department of Comparative Biomedical Sciences, Royal Veterinary College, Hertfordshire, UK.
- Equine Studies Group, Waltham Petcare Science Institute, Leicestershire, UK.
- Department of Clinical Sciences and Services, Royal Veterinary College, Hertfordshire, UK.
Grant Funding
- Royal Veterinary College Mellon Fund
- WALTHAM Petcare Science Institute
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