Effect of Butyric Acid on Apoptosis of Pancreatic β Cells.

Abstract

Objective: Islet β-cell dysfunction and insulin resistance are associated with obesity-associated type 2 diabetes mellitus. Short-chain fatty acids (SCFAs) are important regulatory factors for energy metabolism. We aimed to determine the effects of butyric acid (BA) on β-cell apoptosis in type 2 diabetes.

Methods: A db/db transgenic mouse model and lipopolysaccharide (LPS)-stimulated β-cell model were used to determine the effects of BA on β-cells. The viability and apoptosis of β cells were determined using the MTT assay and flow cytometry, respectively. The expression of inflammatory factors IL-1β, TNF-α, IL-6, and IL-10 was measured using quantitative PCR. Activation of the NF-κB signaling pathway was detected by quantitative PCR and Western blotting. Fasting plasma glucose (FPG), fasting insulin (FINS), total cholesterol (TC), and triglyceride (TG) levels were assessed to evaluate glycolipid metabolism. Intestinal flora and SCFA analyses were performed to explore the changes in the gut microbiota.

Results: Butyric acid treatment notably suppressed LPS-induced expression of pro-inflammatory cytokines and improved β-cell apoptosis. The levels of TC, TG, FPG, and FINS were significantly elevated in diabetic mice and decreased after BA treatment. The expression of the β-cell regulatory genes Maf-A and Foxo1 was notably decreased in diabetes, and BA treatment restored their expression levels.

Conclusions: Butyric acid notably alleviated β-cell apoptosis and the secretion of inflammatory cytokines in diabetes by suppressing NF-κB signaling. Butyric acid improves the intestinal flora of diabetic mice, suggesting its potential as a novel therapeutic agent for diabetes.