Islet perturbations in rats fed a high-fat diet

Area of Science:

• Endocrinology
• Metabolic Research
• Animal Models of Diabetes

Background:

• High-fat diets are known to induce insulin resistance.
• The specific effects of high-fat diets on pancreatic islet function and structure are not fully elucidated.
• Understanding early changes in islet response is crucial for managing metabolic disorders.

Purpose of the Study:

• To investigate the impact of a high-fat diet on islet function and insulin secretion in Sprague-Dawley rats.
• To examine changes in insulin gene expression and islet morphology.
• To assess alterations in islet innervation over time.

Main Methods:

• Rats were fed a high-fat diet for 2, 4, and 8 weeks.
• In vivo insulin response to glucose was measured.
• In vitro studies involved isolated islets incubated with glucose and perifusion experiments.
• Insulin gene expression was analyzed using quantitative in situ hybridization.
• Islet size and innervation (VIP, NPY) were assessed.

Main Results:

• In vivo insulin response to glucose was impaired after 4 and 8 weeks but not 2 weeks.
• In vitro, glucose-stimulated insulin secretion from isolated islets was impaired after 2 weeks.
• Insulin gene expression decreased by 52% after 2 weeks.
• Islet hypertrophy was not observed.
• Islet innervation increased significantly after 2, 4, and 8 weeks.

Conclusions:

• High-fat diet-induced insulin resistance in rats is associated with impaired early glucose-stimulated insulin secretion and reduced insulin gene expression.
• These functional deficits occur within 2 weeks, preceding significant in vivo impairment.
• Increased islet innervation and lack of hypertrophy characterize the islet response to a high-fat diet.