Hypoxylonol F Isolated from Annulohypoxylon annulatum Improves Insulin Secretion by Regulating Pancreatic β-cell Metabolism

Abstract

Insulin plays a key role in glucose homeostasis and is hence used to treat hyperglycemia, the main characteristic of diabetes mellitus. <i>Annulohypoxylon annulatum</i> is an inedible ball-shaped wood-rotting fungus, and hypoxylon F is one of the major compounds of <i>A. annulatum</i>. The aim of this study is to evaluate the effects of hypoxylonol F isolated from <i>A. annulatum</i> on insulin secretion in INS-1 pancreatic β-cells and demonstrate the molecular mechanisms involved. Glucose-stimulated insulin secretion (GSIS) values were evaluated using a rat insulin ELISA kit. Moreover, the expression of proteins related to pancreatic β-cell metabolism and insulin secretion was evaluated using Western blotting. Hypoxylonol F isolated from <i>A. annulatum</i> was found to significantly enhance glucose-stimulated insulin secretion without inducing cytotoxicity. Additionally, hypoxylonol F enhanced insulin receptor substrate-2 (IRS-2) levels and activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway. Interestingly, it also modulated the expression of peroxisome proliferator-activated receptor γ (PPARγ) and pancreatic and duodenal homeobox 1 (PDX-1). Our findings showed that <i>A. annulatum</i> and its bioactive compounds are capable of improving insulin secretion by pancreatic β-cells. This suggests that <i>A. annulatum</i> can be used as a therapeutic agent to treat diabetes.