Abstract
Insulin plays a key role in glucose homeostasis and is hence used to treat hyperglycemia, the main characteristic of diabetes mellitus. Annulohypoxylon annulatum is an inedible ball-shaped wood-rotting fungus, and hypoxylon F is one of the major compounds of A. annulatum. The aim of this study is to evaluate the effects of hypoxylonol F isolated from A. annulatum 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 A. annulatum 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 A. annulatum and its bioactive compounds are capable of improving insulin secretion by pancreatic β-cells. This suggests that A. annulatum can be used as a therapeutic agent to treat diabetes.
Highlights
Diabetes is a common chronic metabolic disease that affects millions of people worldwide and is closely related to modern lifestyle [1]
Our findings showed that A. annulatum and its bioactive compounds are capable of improving insulin secretion by pancreatic β-cells
We found that peroxisome proliferator-activated receptor γ (PPARγ) activation plays a major role in the insulin-secreting effect of hypoxylonol F
Summary
Diabetes is a common chronic metabolic disease that affects millions of people worldwide and is closely related to modern lifestyle [1]. Hyperglycemia is the hallmark of diabetes and is caused by impaired insulin synthesis or secretion [2]. Pancreatic β-cells located in the islet of Langerhans play a critical role in insulin synthesis and secretion, which controls energy metabolism [3]. The elevation in blood glucose levels after a meal stimulates insulin secretion [4]. When insulin secretion is inadequate to meet the metabolic demand, blood glucose levels remain high, resulting in diabetes [5,6].
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