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      A brief review of in vitro models of diabetic neuropathy


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          The neuropathies of the peripheral, central and autonomic nervous systems are known to be caused by hyperglycemia, a consequence of the deregulation of glucose in diabetes. Several in vivo models such as streptozotocin-induced diabetic rats, mice and Chinese hamsters have been used to study the pathogenesis of diabetic neuropathy because of their resemblance to human pathology. However, these in vivo models have met with strong ethical oppositions. Further, the system complexity has inherent limitations of inconvenience of analyzing ephemeral molecular events and crosstalk of signal transduction pathways. Alternative in vitro models have been selected and put to effective use in diabetic studies. We critically review the use of these in vitro models such as primary cultures of dorsal root ganglia, Schwann cells and neural tissue as well as neural cell lines which have proved to be excellent systems for detailed study. We also assess the use of embryo cultures for the study of hyperglycemic effects on development, especially of the nervous system. These systems function as useful models to scrutinize the molecular events underlying hyperglycemia-induced stress in neuronal systems and have been very effectively used for the same. This comprehensive overview of advantages and disadvantages of in vitro systems that are currently in use will be of interest especially for comparative assessment of results and for appropriate choice of models for experiments in diabetic neuropathy.

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          Oxidative stress in the pathogenesis of diabetic neuropathy.

          Oxidative stress results from a cell or tissue failing to detoxify the free radicals that are produced during metabolic activity. Diabetes is characterized by chronic hyperglycemia that produces dysregulation of cellular metabolism. This review explores the concept that diabetes overloads glucose metabolic pathways, resulting in excess free radical production and oxidative stress. Evidence is presented to support the idea that both chronic and acute hyperglycemia cause oxidative stress in the peripheral nervous system that can promote the development of diabetic neuropathy. Proteins that are damaged by oxidative stress have decreased biological activity leading to loss of energy metabolism, cell signaling, transport, and, ultimately, to cell death. Examination of the data from animal and cell culture models of diabetes, as well as clinical trials of antioxidants, strongly implicates hyperglycemia-induced oxidative stress in diabetic neuropathy. We conclude that striving for superior antioxidative therapies remains essential for the prevention of neuropathy in diabetic patients.
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            Multiple neurotransmitter synthesis by human neuroblastoma cell lines and clones.

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              Multilineage differentiation from human embryonic stem cell lines.

              Stem cells are unique cell populations with the ability to undergo both self-renewal and differentiation. A wide variety of adult mammalian tissues harbors stem cells, yet "adult" stem cells may be capable of developing into only a limited number of cell types. In contrast, embryonic stem (ES) cells, derived from blastocyst-stage early mammalian embryos, have the ability to form any fully differentiated cell of the body. Human ES cells have a normal karyotype, maintain high telomerase activity, and exhibit remarkable long-term proliferative potential, providing the possibility for unlimited expansion in culture. Furthermore, they can differentiate into derivatives of all three embryonic germ layers when transferred to an in vivo environment. Data are now emerging that demonstrate human ES cells can initiate lineage-specific differentiation programs of many tissue and cell types in vitro. Based on this property, it is likely that human ES cells will provide a useful differentiation culture system to study the mechanisms underlying many facets of human development. Because they have the dual ability to proliferate indefinitely and differentiate into multiple tissue types, human ES cells could potentially provide an unlimited supply of tissue for human transplantation. Though human ES cell-based transplantation therapy holds great promise to successfully treat a variety of diseases (e.g., Parkinson's disease, diabetes, and heart failure) many barriers remain in the way of successful clinical trials.

                Author and article information

                Int J Diabetes Dev Ctries
                International Journal of Diabetes in Developing Countries
                Medknow Publications (India )
                Oct-Dec 2009
                : 29
                : 4
                : 143-149
                Department of Life Sciences, Sophia College, B. Desai Road, Mumbai - 400 026, India
                Author notes
                Correspondence to Dr. Medha S. Rajadhyaksha, Life Sciences Department, Sophia College, B. Desai Road, Mumbai- 400 026, India. E-mail: medhasr@ 123456rediffmail.com
                © International Journal of Diabetes in Developing Countries

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                : 21 June 2008
                : 12 September 2009
                Review Article

                Endocrinology & Diabetes
                high glucose,diabetic neuropathy,in vitro experimental models
                Endocrinology & Diabetes
                high glucose, diabetic neuropathy, in vitro experimental models


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