Pancreatic α‐cell dysfunction associated with equine insulin dysregulation
Sanna Lindåse, Emma Strage, Josefin Söder, Johan BröjerAbstract
Background
Insulin dysregulation (ID) in horses is characterised by insulin resistance and exaggerated insulin responses, yet the underlying endocrine mechanisms remain incompletely understood. In humans, α‐cell dysfunction characterised by exaggerated glucagon secretion contributes to metabolic disease; however, the role of pancreatic α‐cell function in equine ID has not previously been investigated.
Objectives
To investigate whether horses with moderate to severe ID exhibit α‐cell dysfunction, characterised by fasting and postprandial hyperglucagonaemia as well as impaired postprandial glucagon suppression compared with a cohort of horses with normal insulin regulation (NIR).
Study Design
Cross‐sectional experimental study.
Methods
Insulin dysregulated horses ( n = 19) and NIR horses ( n = 19) underwent a 180‐min seven‐sampled oral sugar test. Plasma glucose, insulin, and glucagon concentrations were measured at baseline and every 30 min for 180 min postprandially. Fasting glucagon concentrations (Fasting GLUCAGON ), total area under the curve for glucagon (AUC GLUCAGON ), and postprandial suppression of glucagon secretion were used as primary outcomes.
Results
Horses with ID exhibited higher geometric mean (95% confidence interval) values compared to NIR horses for the α‐cell dysfunction indices Fasting GLUCAGON (10.3 (8.0–13.4) vs. 4.1 (3.5–4.8) pmol/L, p < 0.0001) and AUC GLUCAGON (1351.5 (1016.1–1797.7) vs. 624.7 (529.8–736.6) pmol/L•min, p < 0.0001). Geometric least squares mean (95% confidence interval) glucagon concentrations were higher ( p = 0.01) at 180 min after oral sugar administration in ID horses (6.3 (5.0–8.0) pmol/L) compared with baseline concentrations in NIR horses (4.1 (3.3–5.2) pmol/L), indicating impaired postprandial glucagon suppression in the ID group.
Main Limitations
Cross‐sectional design and unmatched groups limit causal inference.
Conclusions
Horses with moderate to severe ID exhibit marked α‐cell dysfunction characterised by fasting and postprandial hyperglucagonaemia and impaired postprandial suppression of glucagon secretion. These findings identify α‐cell dysfunction as a novel component of equine ID.