Pancreatic islet remodeling in horses with hyperinsulinemia and pituitary dysfunction.

Overview

• This study investigates the structure and cellular composition of pancreatic islets in healthy horses and how these features change in horses suffering from hyperinsulinemia (HI) and pituitary pars intermedia dysfunction (PPID).
• It demonstrates that HI and PPID cause different adaptations in the pancreatic islets, suggesting distinct mechanisms by which these diseases affect pancreatic function.

Background and Purpose

• The equine pancreas, which plays a critical role in regulating blood sugar, is under-researched, especially regarding its endocrine (hormone-producing) part.
• Pancreatic islets contain different types of hormone-secreting cells: alpha-cells (glucagon), beta-cells (insulin), and delta-cells (somatostatin).
• The study aimed to:
• Characterize the normal distribution and cellular makeup of pancreatic islets in horses.
• Determine how two endocrine disorders—HI and PPID—affect the structure and hormone production of these islets.

Methods

• Two experiments were conducted:
• Experiment 1: Pancreatic tissue from eight healthy horses was sampled from three anatomical regions—the left lobe, body, and right lobe.
• Experiment 2: Pancreas samples from 35 horses with known endocrine disease status were analyzed.
• Measurements included relative islet area, perimeter, cell composition, number of islets, islet size, and insulin expression via immunostaining.

Key Findings in Healthy Horses

• The left lobe of the pancreas has a larger relative islet area and perimeter compared to the body and right lobe.
• Islet cellular composition across all regions was similar, displaying:
• An alpha-cell core.
• A beta-cell mantle surrounding the core.
• Scattered delta-cells interspersed within the islets.
• This establishes a baseline normal architecture and cellular arrangement in the equine pancreas.

Effects of Hyperinsulinemia (HI)

• Horses with HI exhibited larger islets compared to healthy controls.
• There was increased insulin immunostaining, indicating higher insulin content or secretion capability per islet.
• This suggests islet expansion as a compensatory mechanism to overcome insulin resistance commonly associated with HI.
• Such growth likely helps the pancreas maintain adequate insulin levels despite impaired tissue sensitivity.

Effects of Pituitary Pars Intermedia Dysfunction (PPID)

• Unlike HI, PPID was associated with an increased number of islets rather than larger islets.
• Islet size and insulin staining did not significantly change compared to healthy horses.
• This may indicate islet neogenesis (formation of new islets) triggered by chronic endocrine dysfunction.
• The increase in islet number could be a novel response of the pancreas to the altered hormonal environment caused by PPID.

Conclusions and Implications

• The study provides foundational knowledge of regional islet distribution and composition in the equine pancreas.
• HI and PPID induce distinct remodeling processes: islet enlargement and increased insulin production in HI, versus increased islet numbers in PPID.
• These findings highlight the pancreas’ adaptability to chronic endocrine stress through different structural and functional strategies.
• Understanding these mechanisms may improve diagnosis and treatment strategies of equine endocrine diseases and contribute to comparative studies across species.