Rice bran protein hydrolysates attenuate diabetic nephropathy in diabetic animal model.

INTRODUCTION: Diabetic nephropathy (DN) is an important microvascular complication of uncontrolled diabetes. The features of DN include albuminuria, extracellular matrix alterations, and progressive renal insufficiency. Rice bran protein hydrolysates (RBPs) have been reported to have antihyperglycemic, lipid-lowering, and anti-inflammatory effects in diabetic rats. Our study was to investigate the renoprotective effects of RBP in diabetic animals and mesangial cultured cells. METHODS: Eight-week-old male db/m and db/db mice were orally treated with tap water or RBP (100 or 500 mg/kg/day) for 8 weeks. At the end of the experiment, diabetic nephropathy in kidney tissues was investigated for histological, ultrastructural, and clinical chemistry changes, and biomarkers of angiogenesis, fibrosis, inflammation, and antioxidant in kidney were analyzed by Western blotting. Protection against proangiogenic proteins and induction of cytoprotection by RBP in cultured mesangial cells was evaluated. RESULTS: RBP treatment improved insulin sensitivity, decreased elevated fasting serum glucose levels, and improved serum lipid levels and urinary albumin/creatinine ratios in diabetic mice. RBP ameliorated the decreases in podocyte slit pore numbers, thickening of glomerular basement membranes, and mesangial matrix expansion and suppressed elevation of MCP-1, ICAM-1, HIF-1α, VEGF, TGF-ß, p-Smad2/3, and type IV collagen expression. Moreover, RBP restored suppressed antioxidant Nrf2 and HO-1 expression. In cultured mesangial cells, RBP inhibited high glucose-induced angiogenic protein expression and induced the expression of Nrf2 and HO-1. CONCLUSION: RBP attenuates the progression of diabetic nephropathy and restored renal function by suppressing the expression of proangiogenic and profibrotic proteins, inhibiting proinflammatory mediators, and restoring the antioxidant and cytoprotective system.

[A clinico-pathogenetic assessment of the membrane structure and functions of the peripheral blood lymphocytes in insulin-dependent diabetes mellitus]. / Kliniko-patogeneticheskaia otsenka struktury i funktsii membran limfotsitov perifericheskoi krovi pri insulinzavisimom sakharnom diabete.

The structure and functions of lymphocyte membranes with characterization of their phospholipid composition, lipid peroxidation intensity (LP), activity of membranous ATPases and a type of the immune status were investigated in patients with insulin dependent diabetes mellitus. The results obtained were indicative of considerable differences (LP) in the lymphocytes of these patients as compared to those of healthy controls. LP intensity showed correlation with change in the ratio of phospholipid fractions and change in ATPase activity. In complicated insulin dependent diabetes mellitus destabilization of lymphocyte cell membranes and disturbance of transmembranous transport were more marked than in uncomplicated disease. The structure and functions of the membranes of immunocompetent cells, a degree of carbohydrate metabolic decompensation and the presence of complications determined an immune response type.

Assessment of the role of the immunoglobulin isotypes in the development of diabetic nephropathy in untreated streptozotocin-induced diabetic rats.

Thirty of 45 (67%) streptozotocin-induced male Sprague-Dawley diabetic rats developed microalbuminuria that progressed to overt proteinuria with increased concentrations of IgG in their urine. 33% (15/45) never developed albuminuria or IgG proteinuria. These percentages did not correlate with glucose control since none of the animals were treated with insulin and all demonstrated the same degree of hyperglycemia. Indirect immunofluorescent antibody staining of frozen tissue sections from the kidneys of rats that developed overt proteinuria stained for IgM (67%), C3 (93%), IgG2b (93%) and IgG2c (60%). Non-proteinuric diabetic kidneys stained for IgM (80%), C3 (67%) IgG2b (67%) and IgG2c (87%). Control kidney sections demonstrated no consistent staining pattern. The occurrence and concentration of the different immunoglobulin isotypes, eluted from frozen sections with immune complex dissociating buffers, mimicked that which was observed by immunofluorescence. When urine or serum from the same rat or a rat of a different group was incubated with kidney sections eluted of all immunoglobulin, indirect immunofluorescent staining demonstrated antibody activity corresponding to the original staining pattern observed for each animal group prior to elution. The most consistent observation was that the diabetic rats that developed proteinuria were positive for IgG2b staining in their kidney sections; whereas, those that did not develop proteinuria stained predominantly for IgG2c. From this data, we suggest that the progression of diabetic nephropathy may depend on whether a specific IgG subclass response is elicited.