Short‐term induced hyperinsulinaemia and dexamethasone challenge do not affect circulating total adiponectin concentrations in insulin‐sensitive ponies

Abstract

AbstractBackgroundHypoadiponectinaemia is a risk factor for endocrinopathic laminitis, but the directionality and nature of its association with insulin dysregulation is unclear.ObjectivesTo 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.Study designIn vivo experiment.MethodsSix 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.ResultsThere 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.Main limitationsThis was a small sample size that included only native‐breed ponies; total adiponectin was measured rather than high‐molecular‐weight adiponectin.ConclusionsShort‐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.