Soy protein preserves basement membrane integrity through a synergistic effect on nephrin, matrix metalloproteinase and vascular endothelial growth factor.

BACKGROUND/AIMS: Soy protein improves renal function and prevents albuminuria in diabetic rats. This study investigates whether the renoprotective effect of soy protein is related to sustenance of basement membrane integrity. METHODS: Adult male albino rats were randomized into four groups and fed one of the following semi-synthetic diets consisting of corn starch (60%) and casein (20%; CCD), fructose (60%) and casein (20%; FCD), fructose (60%) and soy protein (20%; FSD), or corn starch (60%) and soy protein (20%; CSD). Plasma chemistry and renal changes were analyzed after 60 days. RESULTS: FCD rats displayed metabolic derangements and renal ultrastructural changes. FSD rats showed reduction in type IV collagen, tissue inhibitor for matrix metallo-proteinase-2, vascular endothelial growth factor and tumor necrosis factor-α expression and improved matrix metallo-proteinase expression. Renal architecture was preserved in these rats. CONCLUSION: Soy protein supplementation not only improved insulin sensitivity but also markedly attenuated renal basement membrane changes in fructose diet-fed rats. These findings provide evidence in support of the use of dietary soy protein in patients with diabetic kidney disease.

Genistein modulates NF-κB-associated renal inflammation, fibrosis and podocyte abnormalities in fructose-fed rats.

The study determines the effect of genistein on inflammatory status and expression of nuclear factor-kappa B (NF-κB p65), transforming growth factor-ß1 (TGF-ß1) and receptor for advanced glycation end products (RAGE) in kidney of fructose-fed rats. Adult male Wistar rats were fed a diet containing either starch or fructose as the source of carbohydrate. Fifteen days later, after confirming the development of insulin resistance in fructose-fed rats, the rats in each dietary group were divided into two and treated with either genistein (1 mg/kg/day) in 30% dimethylsulfoxide (DMSO) or 30% DMSO alone for the next 45 days. The expression of NF-κB P(65), TGF-ß1 and RAGE, histochemical localization of α-smooth muscle actin (α-SMA), levels of tumour necrosis factor-α (TNF-α) and interleukin-6(IL-6) and ultrastructural analysis were performed at the end of the experimental period. Fructose-fed rats displayed inflammatory changes in kidney. Increased expression of TGF-ß1 and RAGE in cytosol and NF-κB p65 in nuclear fraction were observed. α-SMA expression was higher in fructose-fed rat kidney. Proliferation of connective tissue was evident from increased collagen deposition in perivascular and intraglomerular regions. Administration of genistein to fructose-fed rats reduced inflammation, fibrogenesis and NF-κB activation. Genistein also mitigated the structural changes such as basement membrane thickening, reduction in podocyte number and loss of glomerular filtration barrier integrity. These findings suggest that genistein prevents inflammation, fibrosis and early nephropathic changes in fructose-fed insulin resistant rats secondary to the attenuation of NF-κB activation.

Renoprotective and blood pressure-lowering effect of dietary soy protein via protein kinase C beta II inhibition in a rat model of metabolic syndrome.

We studied whether substitution of soy protein for casein can improve insulin sensitivity, lower blood pressure (BP), and inhibit protein kinase C betaII (PKCbetaII) activation in kidney in an acquired model of metabolic syndrome. Adult male rats were fed 4 different diets: (i) starch (60%) and casein (20%) (CCD), (ii) fructose (60%) and casein (20%) (FCD), (iii) fructose (60%) and soy protein (20%) (FSD), and (iv) starch (60%) and soy protein (20%) (CSD). Renal function parameters, BP, pressor mechanisms, PKCbetaII expression, oxidative stress, and renal histology were evaluated after 60 days. FCD rats displayed insulin resistance and significant changes in body weight, kidney weight, urine volume, plasma and urine electrolytes accompanied by significant changes in renal function parameters compared with CCD rats. Elevated BP, plasma angiotensin-converting enzyme (ACE) activity, renal oxidative stress, and reduced nitrite (NO) and kallikrein activity were observed. Western blot analysis revealed enhanced renal expression of membrane-associated PKCbetaII in the FCD group. Histology showed fatty infiltration and thickening of glomeruli while urinary protein profile revealed a 5-fold increase in albumin. Substitution of soy protein for casein improved insulin sensitivity, lowered BP and PKCbetaII activation and restored renal function. Antioxidant action, inhibitory effect on ACE and PKCbetaII activation, and increased availability of kinins and NO could be contributing mechanisms for the benefits of dietary soy protein.

Aminoacid support in the prevention of diabetes and diabetic complications.

Emerging evidence suggests that amino acids may be potentially important in the prevention of diabetes and diabetes-associated complications. The pathways involved in the pathogenesis of diabetic complications include increased polyol pathway flux, increased advanced glycation end products formation, activation of protein kinase C and oxidative and carbonyl stress. This review will discuss the modulatory effects of amino acids on insulin secretion and their action in concert with insulin as signaling molecules. Evidences for the role of some amino acids in controlling glycemia and glucose-triggered pathological pathways are also included. Individual amino acids, especially the ones bestowed with antioxidant property like N-acetyl cysteine and taurine seem to have beneficial effects by their ability to reduce intracellular oxidative stress generation and glycooxidation. Other amino acids like glycine and lysine may be good candidates for the prevention of glycation. Nutritional intervention with taurine, phenyl alanine or branched chain amino acids can improve insulin sensitivity and post-prandial glucose disposal. Deficiency of one or more amino acids has been observed in diabetes and the beneficial effects of amino acids in some studies are positively correlated with the increase in plasma levels of these amino acids. Inclusion of individual amino acids/mixture, perhaps as a combinational therapy with conventional treatment protocols could be of therapeutic interest.

Effect of genistein, a soy isoflavone, on whole body insulin sensitivity and renal damage induced by a high-fructose diet.

The study evaluates the effect of genistein, a soy isoflavone, on insulin sensitivity and renal functional and structural injury in rats rendered insulin-resistant by feeding on a high-fructose diet for 60 days. Fructose-fed animals (60 g /100 g) displayed insulin resistance as indicated by the measures of insulin sensitivity [insulin sensitivity index (ISI(0,120)), quantitative insulin check index (QUICKI), and homeostatic model assessment (HOMA)]. Alterations in body weight, kidney weight, urine volume, plasma, and urine electrolytes accompanied by significant increases in plasma and urinary levels of urea, uric acid, creatinine, total protein, and albumin were observed in fructose-fed rats. Oxidative stress in kidney was noted by an elevation in lipid peroxides and a decline in glutathione (GSH). Insulin sensitivity and renal function were improved in fructose-fed rats administered genistein. Histological changes such as fatty infiltration and thickening of glomeruli observed in fructose-fed rats were also ameliorated when genistein was co-administered. The study shows that genistein improves insulin sensitivity and kidney function in a dietary model of insulin resistance. We suggest that genistein may have benefits for patients suffering from kidney disease associated with insulin resistance.

Taurine prevents fructose-diet induced collagen abnormalities in rat skin.

OBJECTIVE: The aim of the study is to investigate the effect of taurine administration on the content and characteristics of skin collagen in high-fructose-fed rats. RESEARCH DESIGN AND METHODS: Adult male Wistar rats were divided into four groups of six each: a control group (CON) and a taurine-supplemented control group (CON+TAU), a high fructose diet-fed group (FRU), and a taurine supplemented fructose diet-fed group (FRU+TAU). After 30 days, collagen was isolated from the skin, and its physicochemical properties were studied. RESULTS: Fructose administration caused an accumulation of collagen and extensive cross-linking. This was evidenced by increases in glycation, fluorescence, and peroxidation in collagen samples. The physicochemical properties of collagen, like shrinkage temperature, aldehyde content, solubility pattern, and susceptibility to denaturing agents, were altered in the fructose-fed rats. The sodium dodecyl sulphate-polyacrylamide gel electrophoretic (SDS-PAGE) pattern of collagen from fructose-fed rats showed and elevated beta component of Type I collagen. Simultaneous administration of taurine alleviated these changes. CONCLUSION: The positive influence of taurine on both collagen content and its properties suggests a potential mechanism for the ability of taurine to delay diabetic complications.

Inhibition of lipid peroxidation, protein glycation and elevation of membrane ion pump activity by taurine in RBC exposed to high glucose.

BACKGROUND: Supplementation of taurine, a sulfur containing amino acid has been found to be beneficial in counteracting oxidative stress and in preventing experimental diabetic neuropathy, nephropathy and retinopathy. Taurine has its own capacity to prevent the suppression of membrane-bound Na(+)/K(+)ATPase activity and prevent Ca(2+) overload. This study was undertaken to test whether taurine can reduce lipid peroxidation and glycosylation and can increase the Na(+)/K(+)- and Ca(2+)-ATPase activities in high glucose-treated red blood cells (RBC). METHODS: Washed normal human RBC were incubated in phosphate-buffered saline with normal (6 mmol/l) or high glucose concentrations (45 mmol/l), with and without 50-150 micromol/l taurine in a shaking water bath at 37 degrees C for 24 h. Lipid peroxidation, glycated hemoglobin, glucose utilization and Na(+)/K(+)- and Ca(2+)-ATPase activities were determined in the glucose-treated human RBC. RESULTS: Taurine significantly lowered the level of glycated hemoglobin (GHb) and lipid peroxidation in RBC exposed to high glucose concentrations. Stimulation of glucose utilization by RBC was significant in the presence of taurine both in normal and high glucose-treated RBC. The activities of Na(+)/K(+)- and Ca(2+)-ATPases in RBC membranes were significantly lowered in high glucose-treated RBC. Taurine treatment significantly prevented the reduction in activities of Na(+)/K(+)- and Ca(2+)-ATPases activities in high glucose-treated RBC. CONCLUSIONS: The results show that taurine is important for the physiological functions of RBCs and the effects of taurine on glucose-treated RBC may have potential therapeutic relevance in diabetes.