Abstract
Significance. With an alarming increase in recent years, diabetes mellitus has become a global challenge. Despite advances in treatment of diabetes mellitus, currently, medications available are unable to control the progression of diabetes and its complications. Growing evidence suggests that inflammation is an important pathogenic mediator in the development of diabetes mellitus. The perspectives including suggestions for new therapies involving the shift from metabolic stress to inflammation should be taken into account. Critical Issues. High-mobility group box 1 (HMGB1), a nonhistone nuclear protein regulating gene expression, was rediscovered as an endogenous danger signal molecule to trigger inflammatory responses when released into extracellular milieu in the late 1990s. Given the similarities of inflammatory response in the development of T2D, we will discuss the potential implication of HMGB1 in the pathogenesis of T2D. Importantly, we will summarize and renovate the role of HMGB1 and HMGB1-mediated inflammatory pathways in adipose tissue inflammation, insulin resistance, and islet dysfunction. Future Directions. HMGB1 and its downstream receptors RAGE and TLRs may serve as potential antidiabetic targets. Current and forthcoming projects in this territory will pave the way for prospective approaches targeting the center of HMGB1-mediated inflammation to improve T2D and its complications.
Highlights
It is reported that there are approximately 10 percent of the adult population suffering from diabetes in the world
High-mobility group box 1 (HMGB1) is a nonhistone chromosomal binding protein mainly located in the nucleus of most tissues, wherein it binds to DNA and regulates chromatin remodeling, DNA damage repair, and gene transcription [16, 17]
These findings suggested that HMGB1 might have an important role in the initiation and development of adipose tissue inflammation
Summary
It is reported that there are approximately 10 percent of the adult population suffering from diabetes in the world. T2D, a metabolic disorder formed after a long and complicate pathological process, is characterized by decreased insulin sensitivity and following pancreatic β-cell dysfunction [2, 3]. After long-term overnutrition, metabolic balance of body is broken and becomes an origination of insulin resistance. Longterm overload of work may result in islet β-cell dysfunction even death. Several metabolic processes, such as endoplasmic reticulum stress, hypoxia, and lipotoxicity, are all involved in overnutrient-induced metabolic inflammation. Obesity and obesity-associated inflammation have long been proposed to be responsible for insulin resistance and T2D [4]. In this review we will focus on the pathophysiological connections between HMGB1 and obesity, insulin resistance, and islet dysfunction. The understanding of the role of HMGB1 may provide a new insight into anti-inflammatory therapeutic strategies for T2D
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