Insulin resistance and pancreaticβ-cell dysfunction are major pathological mechanisms implicated in the development and progression of type 2 diabetes(T2D).Beyond the detrimental effects of insulin resistance,inflamm...Insulin resistance and pancreaticβ-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 defineβ-cell dysfunction.Predominant markers of inflammation such as C-reactive protein,tumor necrosis factor alpha,and interleukin-1βare consistently associated withβ-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 pancreaticβ-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 pathological implications of inflammation and oxidative stress during the development ofβ-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 duringβ-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 improveβ-cell function.展开更多
基金Supported by the Biomedical Research and Innovation Platform,of the South African Medical Research Council (SAMRC)the National Research Foundation (grant No. 132534 and 141929)
文摘Insulin resistance and pancreaticβ-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 defineβ-cell dysfunction.Predominant markers of inflammation such as C-reactive protein,tumor necrosis factor alpha,and interleukin-1βare consistently associated withβ-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 pancreaticβ-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 pathological implications of inflammation and oxidative stress during the development ofβ-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 duringβ-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 improveβ-cell function.
