Potential Biochemical Mechanisms of Lung Injury in Diabetes
Zheng Hong1,2, Wu Jinzi1, Jin Zhen1, Yan Liang-Jun1,*
1Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA 2Department of Basic Theory of Traditional Chinese Medicine, College of Basic Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, 250355, China
Accumulating evidence has shown that the lung is one of the target organs for microangiopathy in patients with either type 1 or type 2 diabetes mellitus (DM). Diabetes is associated with physiological and structural abnormalities in the diabetic lung concurrent with attenuated lung function. Despite intensive investigations in recent years, the pathogenic mechanisms of diabetic lung injury remain largely elusive. In this review, we summarize currently postulated mechanisms of diabetic lung injury. We mainly focus on the pathogenesis of diabetic lung injury that implicates key pathways, including oxidative stress, non-enzymatic protein glycosylation, polyol pathway, NF-κB pathway, and protein kinase c pathway. We also highlight that while numerous studies have mainly focused on tissue or cell damage in the lung, studies focusing on mitochondrial dysfunction in the diabetic lung have remained sketchy. Hence, further understanding of mitochondrial mechanisms of diabetic lung injury should provide invaluable insights into future therapeutic approaches for diabetic lung injury.
Figure 1. Hyperglycemia-upregulated pathways that are potentially involved in diabetic lung injury. These include protein glycation, PKC pathway, NF-KB pathway, polyol pathway, and oxidative stress. It should be noted that these pathways may be inter-related. For example, the polyol pathway can also contribute to oxidative stress.
Figure 2. Possible role of mitochondrial dysfunction in diabetic lung injury. Show is the mitochondrial elements that are involved in cell death. Initial production of mitochondrial ROS can lead to changes in membrane potential and opening of mitochondrial permeability transition pore (MPTP) opening. MPTP opening could further enhance mitochondrial ROS production, forming a vicious cycle that eventually leads to cell death and lung dysfunction.
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