Temporal variation in incretin and insulin secretion in ponies in association with dietary macronutrients.

Overview

• This study investigated how the levels of incretin hormones (GLP-1 and GIP) and insulin vary over a 24-hour period in ponies in relation to their feeding state and diet composition.
• The research explored the connections between these hormones and dietary macronutrients to better understand insulin dysregulation and its potential role in equine metabolic diseases like laminitis.

Background and Rationale

• Equine insulin dysregulation (ID) is a common metabolic condition in horses and ponies that increases the risk of laminitis, a painful hoof disorder linked to excessive insulin levels.
• Incretin hormones—glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)—help regulate insulin secretion in response to food intake, particularly carbohydrates.
• GLP-1 has been implicated in the abnormal insulin responses seen in ID, but the daily patterns of GLP-1, GIP, and insulin, particularly under low-energy feeding, were not previously well understood in ponies.

Objectives

• To measure and describe the temporal changes of GLP-1, GIP, and insulin concentrations in ponies over a 24-hour period.
• To examine how these hormones correlate with dietary macronutrients indirectly measured by blood glucose, total protein, and triglycerides.
• To explore the potential role of GIP in lipid metabolism in ponies and its relationship with insulin dysregulation and metabolic syndrome.

Methods

• Eight healthy ponies were fed a baseline high-fibre diet supplemented with two different types of forage over a 24-hour period.
• Blood samples were collected throughout the day in both fed and unfed states to measure:
• Blood glucose — a marker for carbohydrate metabolism.
• Total protein — indicative of overall nutritional status.
• Serum triglycerides — used as a proxy for fat intake or metabolism.
• GLP-1 and GIP — the incretin hormones.
• Insulin — the hormone regulating glucose uptake and metabolism.
• Statistical analyses examined the temporal variation and correlations among these measures, including time-shift correlations to understand synchronous hormonal changes.
• Additionally, archived samples from a larger cohort of 30 ponies were analyzed to validate findings related to GIP and triglycerides.

Key Findings

• All measured analytes (glucose, total protein, triglycerides, GLP-1, GIP, insulin) showed significant variation over time (P < 0.05), generally peaking after feeding.
• Blood glucose, GLP-1, and insulin concentrations were strongly and synchronously positively correlated, indicating that insulin secretion and GLP-1 release are closely linked to glucose intake and metabolism.
• Unexpectedly, plasma GIP concentrations peaked during the unfed state and showed a trend toward positive correlation with triglyceride levels (r = 0.39; P = 0.08), suggesting a role distinct from glucose-mediated insulin secretion.
• This GIP-triglyceride relationship was confirmed in a larger group of ponies, reinforcing the idea that GIP in ponies may play a role in lipid metabolism and clearance, similar to findings in other species.

Interpretation and Implications

• The strong synchronous relationship between GLP-1, glucose, and insulin supports the role of GLP-1 in stimulating insulin secretion following carbohydrate intake in ponies.
• The peak of GIP in the fasting state and its correlation with triglycerides suggest GIP may have a unique physiological role in fat metabolism in ponies that is different from its classic role in glucose-driven insulin secretion.
• Because obesity is a critical aspect of equine metabolic syndrome, and given GIP’s involvement in lipid handling, further research on GIP’s function could provide insight into the mechanisms of metabolic dysfunction in ponies.
• A better understanding of incretin hormone dynamics could lead to improved management strategies for insulin dysregulation and prevention of laminitis in affected equids.

Conclusions

• The study provides novel temporal profiles of incretin hormones and insulin in ponies relative to feeding and dietary macronutrients.
• It highlights a potential role for GIP in lipid metabolism, opening new avenues for understanding metabolic regulation and dysfunction in ponies.
• These findings contribute to the foundation for future research into equine metabolic disorders and may eventually guide dietary or pharmaceutical interventions to mitigate the risk of laminitis.