Genetics and diet shape the relationship between islet function and whole body metabolism

Area of Science:

• Metabolic research
• Genetics
• Endocrinology

Background:

• Gene-environment interactions are crucial for islet function, yet poorly understood.
• Insulin secretion regulation by genetic background and diet requires further investigation.

Purpose of the Study:

• To investigate how genetic background and diet interact to affect pancreatic islet function and insulin secretion.
• To correlate ex vivo islet function with in vivo metabolic phenotypes.

Main Methods:

• Assessed ex vivo glucose-stimulated insulin secretion and insulin content in islets from 213 mice across 13 strains.
• Mice were fed standard chow, Western diet (WD), or a high-fat, carbohydrate-free (KETO) diet.
• Correlated islet function with in vivo metabolic phenotyping data.

Main Results:

• Significant variation in islet function and insulin phenotypes observed across mouse strains and diets.
• C57BL/6J mice exhibited the least glucose-responsive islets.
• A positive correlation was found between basal and glucose-stimulated insulin secretion, but not insulin content.
• The KETO diet decreased insulin secretion in nearly all strains, alongside increased adiposity and glucose intolerance.
• Glucose tolerance influenced the relationship between ex vivo insulin secretion and plasma insulin levels.

Conclusions:

• Genetic background is a critical factor in determining islet function and response to dietary interventions.
• The KETO diet negatively impacts beta-cell health and overall glucose metabolism, cautioning against its use for pancreatic islet health.
• Dietary interventions should consider the interplay with genetic background for effective metabolic management.