scholarly journals Rice protein ameliorates the progression of diabetic nephropathy in Goto–Kakizaki rats with high-sucrose feeding

2013 ◽  
Vol 110 (7) ◽  
pp. 1211-1219 ◽  
Author(s):  
Masatoshi Kubota ◽  
Reiko Watanabe ◽  
Hideyuki Kabasawa ◽  
Noriaki Iino ◽  
Akihiko Saito ◽  
...  

The effect of rice protein (RP) on diabetic nephropathy in non-obese, spontaneous type 2 diabetic Goto–Kakizaki (GK) rats was investigated. GK rats at 7 weeks of age were fed 20 % RP or casein (C) in standard or high-sucrose diets for 10 weeks. Plasma total cholesterol, TAG, alkaline phosphatase (ALP), adiponectin, creatinine and urinary albumin excretion (UAE) were measured and renal histology was evaluated. Compared with C, RP lowered plasma TAG and improved plasma adiponectin levels in GK rats fed the standard diet (P< 0·05), and also lowered total cholesterol and ALP in high-sucrose-fed GK rats (P< 0·05). RP markedly suppressed the sharp increase in UAE when GK rats were fed high-sucrose diets (P< 0·05), and prevented glomerular mesangial matrix expansion in the deep renal cortex near the corticomedullary junction (P< 0·05). These results strongly indicate that dietary RP can ameliorate the progression of diabetic nephropathy at an early stage compared with C.

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Shaojiang Tian ◽  
Junming Tang ◽  
Huihui Liu ◽  
Liping Wang ◽  
Jianming Shen ◽  
...  

There is growing evidence suggesting that glomerular endothelial cell proliferation and angiogenesis may be responsible for the pathophysiological events in the early stage of diabetic nephropathy. This study was designed to investigate the factors related to glomerular endothelial cell proliferation and glomerular angiogenesis and assess the effect of propyl gallate on preventing these disorders in diabetic rats. We found that glomerular hypertrophy, glomerular mesangial matrix expansion, and albuminuria were significantly increased in DN rats. CD31+ endothelial cells significantly increased in glomerulus of diabetic rats. Double immunofluorescence staining showed some structurally defective vasculus tubes in glomerulus. Real-time PCR and western blot demonstrated the glomerular eNOS expression remained at the same level, while remarkable decreased NO productions and suppressed eNOS activities were observed in diabetic rats. Treatment with propyl gallate improved glomerular pathological changes, reduced endothelial cell proliferation, decreased albuminuria, and restored eNOS activity, but did not alter eNOS expression. These data suggest that endothelial cell proliferation and immature angiogenesis may be the contributors to progression of DN. Propyl gallate is a potential novel therapeutic agent on prevention of diabetic nephropathy.


2020 ◽  
Vol 318 (4) ◽  
pp. F1030-F1040
Author(s):  
Inge Everaert ◽  
Junling He ◽  
Maxime Hanssens ◽  
Jan Stautemas ◽  
Kim Bakker ◽  
...  

Manipulation of circulating histidine-containing dipeptides (HCD) has been shown to affect the development of diabetes and early-stage diabetic nephropathy (DN). The aim of the present study was to investigate whether such interventions, which potentially alter levels of circulating HCD, also affect the development of advanced-stage DN. Two interventions, aerobic exercise training and overexpression of the human carnosinase-1 (hCN1) enzyme, were tested. BTBR ob/ob mice were either subjected to aerobic exercise training (20 wk) or genetically manipulated to overexpress hCN1, and different diabetes- and DN-related markers were compared with control ob/ob and healthy (wild-type) mice. An acute exercise study was performed to elucidate the effect of obesity, acute running, and hCN1 overexpression on plasma HCD levels. Chronic aerobic exercise training did not affect the development of diabetes or DN, but hCN1 overexpression accelerated hyperlipidemia and aggravated the development of albuminuria, mesangial matrix expansion, and glomerular hypertrophy of ob/ob mice. In line, plasma, kidney, and muscle HCD were markedly lower in ob/ob versus wild-type mice, and plasma and kidney HCD in particular were lower in ob/ob hCN1 versus ob/ob mice but were unaffected by aerobic exercise. In conclusion, advanced glomerular damage is accelerated in mice overexpressing the hCN1 enzyme but not protected by chronic exercise training. Interestingly, we showed, for the first time, that the development of DN is closely linked to renal HCD availability. Further research will have to elucidate whether the stimulation of renal HCD levels can be a therapeutic strategy to reduce the risk for developing DN.


2017 ◽  
Vol 68 (7) ◽  
pp. 1449-1452 ◽  
Author(s):  
Raluca Ecaterina Haliga ◽  
Doina Butcovan ◽  
Teodor Oboroceanu ◽  
Alin Constantin Pinzariu ◽  
Victor Vlad Costan ◽  
...  

This study investigated the effects of flaxseed and vitamin E on diabetic nephropathy lesions in an experimental-induced model of diabetes in hamsters. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) in male Golden Syrian hamsters, and diabetic animals were fed either standard diet, or standard diet supplemented with flaxseed (150 g/kg diet), vitamin E (400 mg a-tocopherol/kg diet) or combination of flaxseed and vitamin E in the same dosages, for 20 weeks. Kidney histological evaluation of the diabetic hamsters revealed histological lesions characteristic for diabetic nephropathy, while supplementation of the diet with flaxseed and/or vitamin E improved histological aspects of diabetic nephropathy.


2004 ◽  
Vol 287 (1) ◽  
pp. H135-H148 ◽  
Author(s):  
Tsuneo Kobayashi ◽  
Takayuki Matsumoto ◽  
Kazuyuki Ooishi ◽  
Katsuo Kamata

The aim of the present study was to compare vascular dysfunction between the early (12 wk old) and later (36 wk old) stages of spontaneous diabetes in Goto-Kakizaki (GK) rats. We also evaluated the aortic expression of the α2D-adrenoceptor and endothelial nitric oxide synthase (eNOS). Vascular reactivity was assessed in thoracic aortas from age-matched control rats and 12- and 36-wk GK rats. Using RT-PCR and immunoblots, we also examined the changes in expression of the α2D-adrenoceptor and eNOS. In aortas from GK rats (vs. those from age-matched control rats): 1) the relaxation response to ACh was enhanced at 12 wk but decreased at 36 wk; 2) the relaxation response to sodium nitroprusside was decreased at both 12 and 36 wk, 3) norepinephrine (NE)-induced contractility was decreased at 12 wk but not at 36 wk, 4) the expressions of α1B- and α1D-adrenoceptors were unaffected, whereas those of α2D-adrenoceptor and eNOS mRNAs were increased at both 12 and 36 wk; and 5) NE- and ACh-stimulated NOx (nitrite and nitrate) levels were increased at 12 wk, although at 36 wk ACh-stimulated NOx was lower, whereas NE-stimulated NOx showed no change. These results clearly demonstrate that enhanced ACh-induced relaxation and impaired NE-induced contraction, due to NO overproduction via eNOS and increased α2D-adrenoceptor expression, occur in early-stage GK rats and that the impaired ACh-induced relaxation in later-stage GK rats is due to reductions in both NO production and NO responsiveness (but not in eNOS expression).


Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 457
Author(s):  
Kyeong-Seok Kim ◽  
Jin-Sol Lee ◽  
Jae-Hyeon Park ◽  
Eun-Young Lee ◽  
Jong-Seok Moon ◽  
...  

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.


2006 ◽  
Vol 21 (10) ◽  
pp. 2795-2799 ◽  
Author(s):  
Jun Soma ◽  
Kozo Sato ◽  
Harutaka Saito ◽  
Yoshinori Tsuchiya

2003 ◽  
Vol 284 (6) ◽  
pp. F1138-F1144 ◽  
Author(s):  
Kumar Sharma ◽  
Peter McCue ◽  
Stephen R. Dunn

Diabetic nephropathy is increasing in incidence and is now the number one cause of end-stage renal disease in the industrialized world. To gain insight into the genetic susceptibility and pathophysiology of diabetic nephropathy, an appropriate mouse model of diabetic nephropathy would be critical. A large number of mouse models of diabetes have been identified and their kidney disease characterized to various degrees. Perhaps the best characterized and most intensively investigated model is the db/ db mouse. Because this model appears to exhibit the most consistent and robust increase in albuminuria and mesangial matrix expansion, it has been used as a model of progressive diabetic renal disease. In this review, we present the findings from various studies on the renal pathology of the db/ db mouse model of diabetes in the context of human diabetic nephropathy. Furthermore, we discuss shortfalls of assessing functional renal disease in mouse models of diabetic kidney disease.


2012 ◽  
Vol 90 (2) ◽  
pp. 141-153 ◽  
Author(s):  
Tatyana A. Korolenko ◽  
Fedor V. Tuzikov ◽  
Marina S. Cherkanova ◽  
Thomas P. Johnston ◽  
Natalia A. Tuzikova ◽  
...  

The effects of atorvastatin and carboxymethylated β-glucan (CMG) on the lipoprotein-cholesterol (LP-C) and lipoprotein-triglyceride (LP-TG) fractions and subfractions at the early stage of murine hyperlipidemia, and its pleiotropic anti-inflammatory effects, were studied. Atorvastatin and CMG were administered in ICR male mice with acute lipemia induced with a single injection of poloxamer 407 (P-407). A novel small-angle X-ray scattering method for the determination of fractional and subfractional composition of LP-C and LP-TG was used. In P-407-treated animals, there was a drastic increase of total cholesterol and especially TG. Atorvastatin decreased both the total cholesterol and TG, but not to control levels. CMG primarily decreased TG and was not as potent as atorvastatin. P-407 increased atherogenic LDL-C (IDL-C and LDL1–3-C subfractions) and very low-density lipoprotein-C (VLDL-C) (VLDL1–2-C and VLDL3–5-C subfractions) fractions, with an increase of the total anti-atherogenic HDL-C fraction (HDL2-C subfraction). Atorvastatin treatment of lipemia was followed by a decrease in the total LP-C, total LDL-C (LDL1–3-C subfraction), and the LDL1–3-TG subfraction. Additionally, atorvastatin treatment resulted in an increase in the serum matrix metalloproteases activity both in control and P-407-treated mice. In general, high-dose atorvastatin therapy exerts its lipid-lowering and pleiotropic effects in the early stages of acute lipemia induced in mice by treatment with P-407.


2014 ◽  
Vol 28 (5) ◽  
pp. 604-611 ◽  
Author(s):  
Kento Kitada ◽  
Daisuke Nakano ◽  
Hiroyuki Ohsaki ◽  
Hirofumi Hitomi ◽  
Tohru Minamino ◽  
...  

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Magdy EL Sharkawy ◽  
Samir K Abdul-Hamid ◽  
Tarek T Elmelegy ◽  
Mohammed F Adawy

Abstract Background Diabetes mellitus (DM) is the most frequent cause of chronic kidney failure in both developed and developing countries. Diabetic nephropathy, is a clinical syndrome characterized by albuminuria (&gt;300 mg/day) with permanent and irreversible decrease in glomerular filtration rate (GFR). Aim of the Work To study the role of urinary TNF-α and urine KIM-1 in type 2 diabetic patients as predictors of DN comparative with albuminuria. Patients and Methods This is a cross-sectional study which include 90 type-2 diabetic patients and 30 controls selected from the outpatient clinic of Assiut University hospitals. All patients gave an informed consent and approval for the study was obtained from the IRB committee of the Assiut Medical Faculty. The recruited patients were divided into three groups: Normo-albuminuria Group (A) (n = 30): UACR less than 30 mg/gm, Microalbuminuria Group (B) (n = 30): UACR between 30-299 mg/gm and Macro-albuminuria Group (C) (n = 30): UACR equal or more than 300 mg/gm. Assess Urinary TNF-α and urine KIM-1 in comparision with albuminuria. Results Urinary KIM-1 and urinary TNF-α are statically significant with albuminuria in patients in the early stage of diabetic nephropathy (eGFR _60 mL/min/1.73 m2).Also there are statically significance between patients with macroalbuminuria than microalbuminuria. Conclusion The results of this study recommend the use of KIM-1 and TNF-α as good predictors of early detection of development of diabetic nephropathy.


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