Glucose metabolism via sorbitol pathway has been implicated as a possible contributor to the diabetes-related vascular changes. Nitric oxide plays a major regulatory role in the vascular dilatatory and constricted response. Also it has been observed that diabetes causes vascular changes leading to a decrease in nitric oxide production. Additionally the accumulation of sorbitol is also related t...

Aldose reductase (E.C. 1.1.1.21), an intracellular enzyme of polyol pathway, catalyzes NADPHdependent reduction of glucose to sorbitol. Under normoglycemia, most of the cellular glucose is phosphorylated into glucose-6-phosphate by hexokinase. A minor part of non-phosphorylated glucose enters the polyol pathway, the alternate route of glucose metabolism. However, under hyperglycemia, because of...

We explored the specific impact of polyol pathway hyperactivity on dorsal root ganglia (DRG) using transgenic mice that overexpress human aldose reductase because DRG changes are crucial for the development of diabetic sensory neuropathy. Littermate mice served as controls. Half of the animals were made diabetic by streptozotocin injection and followed for 12 weeks. After diabetes onset, diabet...

We examined the hypothesis that the polyol accumulation resulting from chronic galactose supplementation in the diet produces endoneurial edema that can be prevented by inhibition of aldose reductase. We explored the potential of nuclear magnetic resonance (NMR) spectroscopy to quantitate and characterize the water accumulation in the sciatic nerve in this "galactose neuropathy." The data demon...

Synechocystis sp. strain PCC 6803 GTP cyclohydrolase I and human 6-pyruvoyltetrahydropterin synthase were coexpressed in Escherichia coli. The E. coli transformant produced sepiapterin, which was identified by high-performance liquid chromatography and enzymatically converted to dihydrobiopterin by sepiapterin reductase. Aldose reductase, another indispensable enzyme for sepiapterin production,...