Diabetic neutrophil mitochondrial dysfunction: an inflammatory situation?
Diabetic neutrophil mitochondrial dysfunction: an inflammatory situation?
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DOI：
10.1016/j.freeradbiomed.2011.02.015
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发表时间：
2011-05-15
影响因子：
7.4
通讯作者：
Kevil, Christopher G.
中科院分区：
文献类型：
--
作者：
Bir, Shyamal C.;Kevil, Christopher G.
Despite longstanding research into mechanisms of diabetes pathogenesis, detailed molecular understanding of immune cell dysfunction remains largely unknown. Classification of diabetes mellitus is typically divided into two categories: type 1 diabetes (Insulin Dependent Diabetes Mellitus-IDDM) that encompasses autoimmune attack against pancreatic insulin producing beta cells thus requiring insulin therapy, and type 2 diabetes (Non-Insulin Dependent Diabetes Mellitus-NIDDM) which encompasses a complex set of pathological features including peripheral tissue insulin resistance, impaired regulation of hepatic glucose production, and declining ß-cell function often leading to ß-cell failure. Importantly, type 2 diabetes is intimately linked to obesity due to the newly appreciated relationship between adipose tissue and immune cells which interact to elicit numerous pathophysiological responses such as, insulin receptor desensitization, elevated cytokine production, and dysfunctional glucose metabolism, all known to play an important role in the development and progression of type 2 diabetes [1, 2]. However, the molecular mechanisms involved in immune cell dysfunction during type 2 diabetes remain poorly understood. In this issue of Free Radical Biology and Medicine, a study by Hernadez-Mijares and colleagues examines the phenotype of type 2 diabetic polymorphonuclear leukocytes (PMN’s) with respect to reactive oxygen species (ROS) generation and mitochondrial function revealing a novel and potentially important link between PMN mitochondrial dysfunction and redox imbalance during type 2 diabetes.It is widely accepted that oxidative stress is an important pathophysiological mediator of diabetes development and progression along with associated complications [3]. Given the strong link between diabetes and obesity it stands to reason that increased caloric intake exceeding energy expenditure can lead to mitochondrial electron transport uncoupling permitting the formation of ROS, particularly superoxide anion and hydrogen peroxide (H2O2). ROS are known mediators of oxidative damage to cells that contribute to alterations of insulin/insulin receptor substrate signaling pathways leading to insulin resistance and inflammatory settings [4]. While ROS may be a common pathogenic factor for beta and endothelial cell dysfunction during type 2 diabetes, little specific clinical information exists regarding this relationship with circulating PMN’s in type 2 diabetic patients. In the paper by Hernadez-Mijares et al, diabetic PMN’s had reduced oxygen consumption that was associated with a clear increase in ROS formation. These data indicate that type 2 diabetic leukocytes have defective mitochondrial respiration contributing to intracellular oxidant
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影响因子：
7.7
作者：
Duncan, BB;Schmidt, MI;Heiss, G
通讯作者：
Heiss, G
炎症和代谢疾病中的脂肪因子。
DOI：
10.1038/nri2921
发表时间：
2011-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.1002615
发表时间：
2011-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jagannathan-Bogdan M;McDonnell ME;Shin H;Rehman Q;Hasturk H;Apovian CM;Nikolajczyk BS
通讯作者：
Nikolajczyk BS
DOI：
10.1152/ajpgi.00089.2010
发表时间：
2010-09-01
影响因子：
4.5
作者：
Ivison, Sabine M.;Wang, Ce;Steiner, Theodore S.
通讯作者：
Steiner, Theodore S.
DOI：
10.1111/j.1749-6632.2010.05627.x
发表时间：
2010-01-01
期刊：
MITOCHONDRIAL RESEARCH IN TRANSLATIONAL MEDICINE
影响因子：
--
作者：
Smith, Robin A. J.;Murphy, Michael P.
通讯作者：
Murphy, Michael P.