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High-protein diets exacerbate glomerular hyperfiltration and the progression of diabetic nephropathy. The purpose of this study was to determine whether amino acids also produce nonhemodynamic injury in the glomerulus. When rat mesangial cells were cultured with an amino acid mixture designed to replicate the composition in plasma after protein feeding,(More)
BACKGROUND/AIMS High levels of glucose and/or amino acids increase advanced glycation end products (AGE) and activate protein kinase C (PKC), a key signal for injury in mesangial cells. The aim was to determine whether oxidative stress mediates bidirectional interactions between AGE and PKC ('cross-activation') in this model. METHODS Rat mesangial cells(More)
Microalbuminuria has been associated with cardiovascular risk factors, events, and mortality. It also clusters with hyperinsulinemia and the metabolic syndrome. How urinary albumin excretion and the fasting serum insulin level relate to coronary artery disease (CAD) has not been previously determined. In 308 patients undergoing elective coronary(More)
BACKGROUND Overfeeding amino acids (AAs) increases cellular exposure to advanced glycation end-products (AGEs), a mechanism for protein intake to worsen diabetic kidney disease (DKD). This study assessed receptor for AGE (RAGE)-mediated apoptosis and inflammation in glomerular cells exposed to metabolic stressors characteristic of high-protein diets and/or(More)
BACKGROUND High protein diets and diabetes increase renal renin angiotensin system (RAS) activity, which is associated with glomerular injury. Aminopeptidase A (APA) is a cell surface metalloprotease that degrades angiotensin II (AII) in the mesangium. Mesangial cells (MC) also possess receptors for AII; the type 1 (AT1 receptor) promotes proliferation and(More)
Increased dietary protein and circulating amino acids raise glomerular filtration rate (GFR) and pressure. In diabetes, this glomerular hyperfiltration response is augmented. The purpose of this study was to determine whether glucagon mediates the augmented GFR response to amino acids in diabetes and whether the responses to amino acids and glucagon depend(More)
BACKGROUND In diabetes, high intake of dietary protein exacerbates responses associated with kidney damage. Increased levels of amino acids could injure cells by providing free amino groups for glycation reactions leading to advanced glycation end products (AGEs). METHODS Rat mesangial cells were cultured with increased amino acids designed to resemble(More)
Inflammatory pathways are central mechanisms in diabetic kidney disease (DKD). Serum amyloid A (SAA) is increased by chronic inflammation, but SAA has not been previously evaluated as a potential DKD mediator. The aims of this study were to determine whether SAA is increased in human DKD and corresponding mouse models and to assess effects of SAA on(More)
IN BRIEF Current therapeutic approaches are only moderately efficacious at preventing the progression of diabetic kidney disease (DKD). As the number of people with DKD continues to rise worldwide, there is an urgent need for novel therapies. A better understanding of the root causes and molecular mechanisms of DKD pathogenesis has enabled the(More)
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