The HDAC Inhibitor Butyrate Impairs β Cell Function and Activates the Disallowed Gene Hexokinase I

Area of Science:

• Endocrinology
• Molecular Biology
• Cell Biology

Background:

• Histone deacetylase (HDAC) inhibitors, including butyrate, show promise in reducing diabetes risk and protecting pancreatic beta cells in animal models.
• However, in vitro studies indicate that butyrate can impair insulin secretion from beta cells.

Purpose of the Study:

• To investigate the effects of butyrate on insulin secretion and gene expression in BRIN BD-11 rat pancreatic beta cells.
• To explore the dose-dependent and duration-dependent effects of butyrate on beta cell function.

Main Methods:

• Treatment of BRIN BD-11 cells with varying concentrations (5 mM) and durations of butyrate or trichostatin A.
• Assessment of basal and stimulated insulin secretion, insulin content, and gene expression (hexokinase I, TXNIP).

Main Results:

• Robust HDAC inhibition (5 mM butyrate or trichostatin A for 24 h) decreased basal and stimulated insulin secretion and insulin content.
• Butyrate treatment increased the expression of hexokinase I and TXNIP, potentially impairing insulin secretion and increasing oxidative stress.
• Low-dose and acute high-dose butyrate treatments enhanced nutrient-stimulated insulin secretion.

Conclusions:

• Potent HDAC inhibition impairs in vitro pancreatic beta cell function, contrary to in vivo observations.
• Chronic low-dose and acute high-dose butyrate treatments may better represent the in vivo effects of HDAC inhibition on beta cells.