%0 Journal Article
%T L-Arginine Supplementation in Type II Diabetic Rats Preserves Renal Function and Improves Insulin Sensitivity by Altering the Nitric Oxide Pathway
%A Taylor Claybaugh
%A Sarah Decker
%A Kelly McCall
%A Yuriy Slyvka
%A Jerrod Steimle
%A Aaron Wood
%A Megan Schaefer
%A Jean Thuma
%A Sharon Inman
%J International Journal of Endocrinology
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/171546
%X Rat studies demonstrated that type II diabetes mellitus (T2DM) decreases both the production and bioavailability of nitric oxide (NO). L-arginine (LA) provides the precursor for the production of NO. We hypothesized that LA dietary supplementation will preserve NO production via endothelial nitric oxide synthase (eNOS) causing renal microvascular vasodilation and increased glomerular blood flow and thus increasing glomerular filtration rate (GFR). This would impede the formation of reactive oxygen species which contributes to cell damage and death. LA supplementation preserved GFR in the treated diabetic rats compared to untreated diabetic rats. We provide evidence that this effect may be due to increased levels of eNOS and urinary cyclic guanosine monophosphate, which leads to renal microvascular vasodilation. Plasma nitrotyrosine was decreased in the LA treated rats; however, plasma nitrite levels remained unaffected as expected. Marked improvements in glucose tolerance were also observed in the LA treated diabetic rats. These results demonstrate that LA supplementation preserves NO activity and may delay the onset of insulin resistance and renal dysfunction during hyperglycemic stress. These results suggest the importance of the NO pathway in consequent renal dysfunction and in the development of insulin resistance in diabetic rats. 1. Introduction Diabetic nephropathy is the number one cause of end-stage renal failure [1]. The pathogenesis of diabetic nephropathy is thought to occur in two major stages. First, there is a vasodilation in the pre- and postglomerular arterioles, which leads to higher intraglomerular blood flow and pressure. This causes an early hyperfiltration in the nephrons and eventually damages the glomerular membrane and allows for proteins, glucose, and other molecules to be filtered by the glomerulus and then excreted in the urine. Secondly, the final irreversible stage is a vasoconstriction of the glomerular arterioles, which results in low blood flow and glomerular filtration rates [2]. The nitric oxide (NO) system has been shown to be altered in diabetes and in diabetic nephropathy [3]. Nitric oxide is a vasodilator and if it is deficient or its metabolism is altered, this affects renal function and insulin sensitivity [4]. The precursor for NO is L-arginine (LA). LA is an amino acid that is synthesized within the body and can also be found in various types of food. LA is converted to NO by nitric oxide synthase (NOS) [5]. Endothelial NOS (eNOS) results in NO release from the endothelium of blood vessels and causes
%U http://www.hindawi.com/journals/ije/2014/171546/