Endocrine Abstracts

Background: Endocrinopathic laminitis is a painful equine condition that may cause persistent lameness warranting euthanasia. Hypoadiponectinemia and insulin dysregulation (ID, manifesting as hyperinsulinemia, tissue insulin resistance (IR), and/or excessive insulin responses to non-structural carbohydrates) are independently associated with increased laminitis risk, although underlying mechanisms remain unclear.

Methods: This study aimed to investigate the relationship between adiponectin and ID. Two forms of short-term ID were induced in healthy insulin-sensitive ponies (n=6; four mares, two geldings; 6-18 years; 210-420 kg). Tissue IR was induced via intravenous administration of dexamethasone (0.08 mg/kg) with blood samples collected every 15 min over 3 h. Fourteen days later, hyperinsulinemia was induced for 9 h via euglycemic-hyperinsulinemic clamp, with blood samples collected every 30 min. Insulin and adiponectin concentrations were measured using validated assays and gene expression (adiponectin receptors [AdipoR] 1 and 2, insulin receptor, insulin-like growth factor 1 receptor [IGF-1R]) was assessed via qPCR. Finally, whole-blood was incubated with 10, 100, and 1000 ng/mL dexamethasone for 3 h at 37°C to investigate its direct effect on AdipoR1 and IGF-1R gene expression.

Results: Induced tissue IR did not alter circulating insulin or adiponectin concentrations at any time-point, but significantly upregulated AdipoR1 (two-fold, P<0.01) and IGF-1R (four-fold, P<0.05) expression at 150 and 180 min. Ex vivo incubation with dexamethasone did not cause similar upregulation, confirming the observed changes were not a direct effect of dexamethasone on leucocytes. There was no change in adiponectin concentrations or gene expression associated with induced hyperinsulinemia (serum insulin: 689.08 ± 172.36 mIU/mL).

Conclusion: Short-term induced hyperinsulinemia and tissue IR did not affect circulating adiponectin concentrations in metabolically healthy ponies. However, tissue IR caused upregulation of two receptors linked to adiponectin signalling. The effect of longer-term ID (including excessive insulin responses to carbohydrates) on adiponectin signalling requires further research.