| Abstract: |
The life span and quality of life for diabetic patients are adversely affected mostly by systemic vascular injuries leading to nephropathy, retinopathy, neuropathy, and cardiovascular pathologies (Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, 2003).Thus, it is of great clinical importance to develop therapeutic agents that can prevent vascular damage in diabetic patients, even in the presence of hyperglycemia. Over the last 20 years, there have been numerous studies on the molecular pathogenesis of diabetic vasculopathy (American Diabetes Association, 2005).PKC is a family of serine/ threonine kinases that consist of 10 isoforms. They are separated into three categories based on their structure and regulation, including conventional PKCs (α, β 1, β2 and γ), novel PKCs (δ, ε, η/L and θ), and atypical PKCs (ζ and ι/λ) (Sheetz and King, 2002).Since we originally proposed that hyperglycemia can induce PKC activation, especially the PKC β isoforms, a large number of studies have confirmed that PKC β isoforms are activated chronically in vascular tissues, including the retina, heart, aorta, renal glomeruli, and circulating monocytes in diabetic patients and animals. (Inoguchi et al 2005).Ruboxistaurin, a PKC β isoform selective inhibitor, displayed a 50-fold higher selectivity for PKC β over other isoforms tested (Ziyadeh et al, 2003).Over the next few years, we should have several new therapeutic compounds for diabetes complications that are derived from a basic understanding of vascular biology of diabetes complications. As for ruboxistaurin, we are cautiously optimistic, but clearly, more large studies are needed to establish its efficacy for treatment of vascular complications in diabetic patients (American Diabetes Association, 2005).
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