Genetical Abnormality and Glucotoxicity in Diabetes Mellitus: The Background of Tissue Damage and Infection

Manaf, Asman (2008) Genetical Abnormality and Glucotoxicity in Diabetes Mellitus: The Background of Tissue Damage and Infection. In: Perhimpunan Dokter Paru Indonesia, Pekanbaru, Riau.

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Abstract

In fact, it will be difficult to define association of diabetes mellitus ( DM ) and infection, include caused by mycobacterial. There are so many factors could be influenced in this process. Firstly, the qualiity of cellular protection, either polymorphonuclear ( PMN ) cells or monocytes is decreased in diabetes mellitus. Mobilization and chemotaxis of PMN in diabetes mellitus is reduced and depressed. Phagocytosis is diminished and impaired PMN adherence is seen in diabetic patients. So, the bactericidal function of PMNs from infected patients with diabetes mellitus is depressed. In the other hand, total number of circulating monocytes is decreased and display impaired monocyte chemotaxis and diminished phagocytosis of microorganism. Monocytes of diabetic patients report upregulated secretion of inflammatory mediators such as TNF-α, IL-1, dan PGE2. Almost all of those abnormalities improved after the patients’ glucose level are controlled. Secondly, the phenomenon of adverse effects of hyperglycemia on insulin target tissue and on pancreatic β cells has been termed “glucotoxicity”. Many evidences exist about the plasma concentrations of glucose, and duration of exposure which can cause clinically significant tissue damage It has been well characterized four major molecular signaling mechanisms activated by hyperglycemia in endothelial cells and other cell types vulnerable to hyperglycemic injury. These include activation of protein kinase C ( PKC ), via diacylglycerol, increased hexosamine pathway flux, increased advanced glycation end products ( AGEs ) formation, and increased polyol pathway flux. Increased production of reactive oxygen species ( ROS ), specifically superoxide, by the mitochondrial electron transport chain, will be a common unifying mechanism that integrates the above pathways. The immunological aspects that growth dynamically and interdependently, and impaired microcirculatory function based on endothelial damages in hyperglycemic state, facilitate the infections in diabetes mellitus. Both genetic determinants and independent accelerating factors play the main role in infection process in DM. Keywords: diabetes, immunological aspects, glucotoxicity, tissue damage, mycobacterial infection.

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