The role of endoplasmic reticulum stress in gut-pancreas axis dysfunction in type 2 diabetes
Type 2 diabetes mellitus(T2DM)is a complex metabolic disorder characterized by chronic hyperglycemia,hyperlipidemia,and peripheral insulin resistance.Endoplasmic reticulum stress(ERS),a response to cellular stress,is activated across various tissues during the progression of T2DM,leading to disruptions in protein synthesis.Notably,epithelial and endocrine cells with hormone-secreting functions are particularly vulnerable to functional impairments induced by ERS.The gut-pancreas axis is essential for regulating metabolism and the progression of T2DM.Intestinal epithelial L cells,integral to the intestinal barrier,can secrete the glucagon-like peptide-1(GLP-1).This hormone promotes insulin secretion from pancreatic β-cells and plays a critical role in glucose metabolism.Importantly,ERS plays a critical role in regulating glucolipid-induced dysfunction of gut-pancreas axis.For instance,ERS is involved in regulating the intestinal barrier and the secretion of GLP-1 as well as insulin.Therefore,ERS can be a potential target for T2DM treatment.In this paper,we review the regulatory roles of ERS in the gut-pancreas axis during the development of T2DM,and summarize the therapeutic drugs and strategies targeting ERS for T2DM treatment.
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