Beta-Hydroxybutyrate Promotes Basal Insulin Secretion While Decreasing Glucagon Secretion in Mouse and Human Islets

Area of Science:

• Endocrinology
• Metabolic Science
• Molecular Biology

Background:

• Dietary carbohydrates impact blood glucose and type 2 diabetes management.
• Low carbohydrate intake promotes fat utilization and ketone production, including beta-hydroxybutyrate (βHB).
• The direct effects of βHB on pancreatic islet cell function are not well understood.

Purpose of the Study:

• To investigate the effects of beta-hydroxybutyrate (βHB) on human islet cell secretory response.
• To determine the specific roles of R-βHB and S-βHB enantiomers on insulin and glucagon secretion.
• To explore the molecular mechanisms underlying βHB's influence on islet cells.

Main Methods:

• Acute treatment of human and mouse islets with racemic βHB and individual enantiomers (R-βHB, S-βHB).
• Measurement of insulin and glucagon secretion at varying glucose concentrations.
• Proteomic analysis of human islets treated with R-βHB over 72 hours.

Main Results:

• Acute βHB treatment increased insulin secretion at low glucose (3 mM) in human islets.
• R-βHB enantiomer specifically increased insulin secretion and decreased glucagon secretion in human and mouse islets at physiological glucose levels.
• Proteomic analysis revealed altered protein abundance in R-βHB treated islets, potentially promoting cell health and survival.

Conclusions:

• Physiological concentrations of βHB, particularly R-βHB, directly influence hormone secretion from pancreatic islets.
• βHB affects both insulin and glucagon release, suggesting a regulatory role in glucose homeostasis.
• R-βHB may contribute to islet cell health and survival, warranting further investigation for therapeutic potential in diabetes.