Metabolic Programming of β-Cell Fate, State, and Function through Time and Space.

Area of Science:

• Endocrinology
• Metabolic Biology
• Stem Cell Biology

Background:

• Beta-cells (β-cells) regulate glucose homeostasis through insulin secretion.
• β-cells transition between proliferation, differentiation, and maturation, impacting function across lifespan.
• Distinct metabolic programs are essential for β-cell state transitions from immaturity to maturity.

Purpose of the Study:

• To outline the known and unknown metabolic physiology of β-cells during development.
• To understand how metabolic programs influence β-cell state transitions.
• To identify strategies for accelerating β-cell maturation and improving diabetes therapies.

Main Methods:

• Review of existing literature on β-cell development in vivo and in vitro.
• Analysis of transcriptional, nutritional, hormonal, and stress-based cues regulating β-cell development.
• Comparison of native β-cell development with human pluripotent stem cell (hPSC)-derived β-like cells.

Main Results:

• β-cell state transitions (proliferation, differentiation, maturation) are energy-dependent.
• Metabolic programming is critical for β-cells to adopt specific functional states.
• hPSC-derived β-like cells exhibit functional immaturity compared to native β-cells.

Conclusions:

• Understanding β-cell metabolic physiology is key to addressing functional immaturity.
• Metabolic insights can guide strategies to enhance β-cell maturation for therapeutic applications.
• Further research into β-cell metabolism is needed to improve diabetes treatment and cell-based therapies.