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Enhanced formation and accumulation of advanced glycation endproducts (AGE's) have been proposed to play a major role in the pathogenesis of diabetic complications, aging, atherosclerosis, and Alzheimer disease leading to progressive and irreversible intermolecular protein crosslinkings. This process is accelerated in diabetes and has been postulated to(More)
Standardized assessment of islet quality is imperative for clinical islet transplantation. We have previously shown that the increment in oxygen consumption rate stimulated by glucose (DeltaOCR(glc)) can predict in vivo efficacy of islet transplantation in mice. To further evaluate the approach, we studied three factors: islet specificity, islet composition(More)
To examine potential mechanisms for the blood pressure-lowering action of the thiazolidinedione compound, pioglitazone (PIO), we studied the effects of the drug on blood pressure and insulin action in vivo and on vascular tissue in vitro. In vivo, PIO lowered blood pressure in fructose-fed and chow-fed rats to an extent that could not be explained by(More)
In addition to inhibiting matrix metalloproteinase-2 and matrix metalloproteinase-9 activity, recent studies suggest that tissue inhibitor of metalloproteinase (TIMP)-1 may inhibit apoptosis in various cell lines. To address this question in pancreatic islets and beta-cells, we treated rat pancreatic islets and INS-1 cells with a high-dose combination of(More)
Insulin secretion and insulin action were studied in rats fed either a diet containing (as percent of calories) 66% fructose, 22% protein, and 12% fat, or standard rat chow (60% vegetable starch, 29% protein, 11% fat) for 7 days. Plasma glucose concentration following either an oral glucose or fructose load (180 mg/100 g body weight) were slightly higher in(More)
BACKGROUND Diabetic retinopathy is associated with accumulation of advanced glycation end products in the retinal microvasculature. LR-90 is an effective multistage inhibitor of advanced glycation with renoprotective and anti-inflammatory properties. AIM To explore the role of LR-90 in the progression of experimental diabetic retinopathy. METHODS(More)
Advanced glycation and lipoxidation endproducts have been implicated in the pathogenesis of diabetic complications, including diabetic nephropathy. LR-90, a new advanced glycation endproduct inhibitor, was investigated for its effects on the development of renal disease in diabetic rats. Diabetic animals were randomly allocated into groups receiving LR-90(More)
The 12-lipoxygenase (LO) pathway of arachidonic acid plays an important role in angiotensin II (AII)-mediated aldosterone synthesis. Several distinct isoforms of 12-LO have been cloned. However, in humans only the platelet form of 12-LO has been reported to be present. Western immunoblotting analysis in cultured human adrenal glomerulosa cells using(More)
Enhanced formation and accumulation of advanced glycation end products (AGEs) have been proposed to play a major role in the pathogenesis of diabetic complications, and atherosclerosis, leading to the development of a range of diabetic complications including nephropathy, retinopathy and neuropathy. Several potential drug candidates as AGE inhibitors have(More)
The leukocyte type of 12-lipoxygenase (12-LO) may play a role in inflammatory reactions in many cell types through the conversion of arachidonic acid to proinflammatory eicosanoids that include 12-hydroperoxyeicosatetraenoic acid and 12-hydroeicosatetraenoic acid. Previous studies demonstrating the presence of a functional 12-LO pathway in rat and human(More)