Abstract
The long-term complications of diabetes remain a major public health issue. Over the last decade, many of the biochemical pathways by which hyperglycemia may cause cellular damage have been studied. These include increased polyol pathway and associated changes in intracellular redox state, increased diacylglycerol synthesis with consequent activation of specific protein kinase C isoforms, increased nonenzymatic glycation of both intra-and extracellular proteins, and increased oxidative stress (1–11). Tissue injury then results from acute changes in protein function and chronic changes in protein expression. However, the molecular pathophysiology of altered membrane function and gene expression leading to tissue injury is still unclear. Type 1 diabetics frequently experience ketosis (hyperketonemia) because, in a state of insulin deficiency, body fuel is derived mainly from fat (12). The blood concentration of ketone bodies may reach 10 mM in diabetics with severe ketosis, compared with concentrations of less than 0.5 mM in normal individuals (12). It is known that ketosis can accelerate microangiopathy and underlying vascular disease and precipitate neuropathy in patients with long-duration diabetes (12). However, the underlying mechanisms by which ketosis promotes vascular disease in type 1 diabetic patients are unclear This chapter is focussed on the mechanisms that underlie the accelerated vascular disease and mortality in diabetic patients. To better differentiate among the complex interactions of various cell types, hormones and dynamic changes in the blood, we have used a cell culture model to accomplish the stated objectives. Specifically, this review discusses whether ketosis increases cellular oxidative stress/damage, and thereby promotes cell surface changes and adhesion between the monocytes and endothelial cells, a crucial step in the pathogenesis of vascular disease in diabetes.
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Jain, S.K., Kannan, K. (2001). Ketosis and the Generation of Oxygen Radicals in Diabetes Mellitus. In: Angel, A., Dhalla, N., Pierce, G., Singal, P. (eds) Diabetes and Cardiovascular Disease. Advances in Experimental Medicine and Biology, vol 498. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1321-6_28
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DOI: https://doi.org/10.1007/978-1-4615-1321-6_28
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