Pancreatic β-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress

Abstract

Insulin resistance and pancreatic β-cell dysfunction are major pathological mechanisms implicated in the development and progression of type 2 diabetes (T2D). Beyond the detrimental effects of insulin resistance, inflammation and oxidative stress have emerged as critical features of T2D that define β-cell dysfunction. Predominant markers of inflammation such as C-reactive protein, tumor necrosis factor alpha, and interleukin-1β are consistently associated with β-cell failure in preclinical models and in people with T2D. Similarly, important markers of oxidative stress, such as increased reactive oxygen species and depleted intracellular antioxidants, are consistent with pancreatic β-cell damage in conditions of T2D. Such effects illustrate a pathological relationship between an abnormal inflammatory response and generation of oxidative stress during the progression of T2D. The current review explores preclinical and clinical research on the patho-logical implications of inflammation and oxidative stress during the development of β-cell dysfunction in T2D. Moreover, important molecular mechanisms and relevant biomarkers involved in this process are discussed to divulge a pathological link between inflammation and oxidative stress during β-cell failure in T2D. Underpinning the clinical relevance of the review, a systematic analysis of evidence from randomized controlled trials is covered, on the potential therapeutic effects of some commonly used antidiabetic agents in modulating inflammatory makers to improve β-cell function.

Keywords: Type 2 diabetes; Insulin resistance; β-cell dysfunction; Inflammation; Oxidative stress

Core Tip: Elevated markers of inflammation and oxidative stress are related to β-cell dysfunction, the intracellular defense (antioxidant) mechanisms responsible for ameliorating some of these effects are significantly depleted during type 2 diabetes (T2D). Thus, beyond lowering glucose levels like most antidiabetic drugs, future research should invest in developing therapeutic agents to ameliorate inflammation and oxidative stress to improve blood control in patients with T2D.