scholarly journals Protective Effects of Adiponectin Against Diabetic Renal Injury in a Mouse Model of Diabetes

2017 ◽  
Vol 43 (2) ◽  
pp. 870-878 ◽  
Author(s):  
Jiacai Hu ◽  
Junjun Dong ◽  
Zhijie Yang ◽  
Hao Wu ◽  
Na Yang

Background/Aims: Adiponectin (Apn) has shown anti-diabetic and anti-inflammatory potential. In the study, we studied and tested the protective effects of Apn against diabetic renal injury and the possible mechanism of these effects. Methods: After 1 week of adaptive feeding, 30 mice were randomly divided into 5 groups: the control group, the model group, the Apn (L) group, the Apn (M) group and the Apn (H) group. All mice were marked and weighed. Following 4 weeks of a pro-diabetic high-fat diet, the model group and Apn groups were injected intraperitoneally with a high dose of STZ (85 mg/kg), while the normal control group was injected with sodium citrate. Fasting blood glucose was measured daily, starting 3 days after STZ injection. After confirming the success of the diabetic model by measuring blood glucose of more than 16.7 nM for 3 successive days, we observed the animal models for an additional 4 weeks. After body weights were measured, urinary albumin, urinary protein, SOD activity and malondialdehyde (MDA) were measured by ELISA, BCA and biochemical assay respectively . Moreover, plasma insulin was assayed by radioimmunoassay, insulin expression in pancreatic β cells was assayed by immunohistochemistry and receptor for advanced glycation end products (RAGE) and corresponding PKC and PKA signaling in the kidney cortex were also assayed by Western blot and Real-time PCR. Results: The results showed that Apn can significantly reduce MDA and enhance SOD activity. Moreover, Apn promoted the synthesis and secretion of insulin by islet β-cells and reduced RAGE accumulation in the kidney, which was associated with down-regulated PKC expression and upregulated PKA expression. Conclusion: Apn has protective effects against hyperglycemia and can effectively enhance antioxidation, promote the secretion of insulin and reduce the accumulation of glycosylated products in T2DM mice; these effects were associated with inhibition of PKC and promotion of PKA signaling.

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Zehui Jiang ◽  
Jun Zhang ◽  
Yuanan Lu

Objective. To explore the protective effect and mechanism of rosuvastatin on acute renal injury induced by a nonionic hypotonic contrast medium in rats. Methods. Forty-eight healthy adult SD rats were randomly divided into three groups: normal control group (NC); contrast medium control group (CM); and rosuvastatin intervention group (RI). The RI group was intragastrically administered with a 10 mg/kg of rosuvastatin 12 h prior to the contrast exposure. All rats in CM and RI groups were inoculated with 10 mL/kg of chemical (IV) while the same volume of saline for the NC group. At 24 h and 72 h posttreatments, pathomorphological changes of renal tubules were documented, respectively, and several biochemical indicators were tested to assess renal injury of experimental rats. Results. Compared with the CM group, rats in the RI group showed significantly reduced injury of kidneys and decreased levels of biochemical indicators such as blood Scr, blood Cys-C, urine NAG, urine α1-MG, and urine mALB. The serum Hs-CRP in the CM group increased significantly from 24 h to 72 h (p<0.05), but this was not observed in the rats of the RI group. In addition, SOD activity in the RI group was significantly increased (p<0.01) while SOD activity in renal tissue decreased significantly with time in the CM group (p<0.05). Conclusion. Short-term intervention with rosuvastatin can lead to reduced kidney damage associated with the contrast agent by reducing the levels of inflammatory factors and oxidative stress. Thus, rosuvastatin intervention has a protective effect on rats from contrast-induced nephropathy.


2018 ◽  
Vol 7 (4.26) ◽  
pp. 136
Author(s):  
Irfiansyah Irwadi ◽  
Hayuris Kinandita ◽  
Jamaluddin Mahmud ◽  
Lilik Herawati

Aim: Antioxidants, such as vitamin C and vitamin E, is widely used as supplements. The aim of this study is to analyze the profile of blood glucose, serum insulin, and  HOMA in active teenagers after vitamin C and vitamin E supplementation.Methods: Subjects (14-16 y.o) consisted of 12 boys and 5 girls, divided into 3 groups: control (4 boys, 2 girls), ‘moderate dose’ of vitamin C and vitamin E combination group (5 boys, 1 girls), and ‘high dose’ of vitamin C and vitamin E combination group (3 boys, 2 girls). The treatment was given for 5 days. Vitamin C and vitamin E for ‘moderate dose’ was 500mg;  200IU, and for ‘high dose’ was 1000mg; 400IU. Fasting Blood Glucose (FGB) and 1 hour BG (1hr_BG), fasting serum insulin (FSI) and 1 hour SI (1hr_SI) was collected after treatment. We also calculated the HOMA-IR and HOMA-β.Result: There was no significant difference on FBG, 1hr_BG, FSI, 1hr_SI, HOMA-IR, and HOMA-β (p≥ 0.05). However, mean FBG and 1hr_BG tended to be higher on the treatment groups. The control group had the lowest HOMA-IR and the highest HOMA-β.Conclusions: We suggest that the supplementation of vitamin C and vitamin E in active teenagers is not essential on glucose homeostasis.  


2018 ◽  
Vol 7 (2) ◽  
pp. 202
Author(s):  
Olivia Herliani

In diabetes mellitus there is an increase in oxidative stress in which oxidants exceed the antioxidant system resulting from the production of oxidant-antioxidant imbalance and/or limited antioxidant defenses. Abelmoschus esculentus (“okra”) is known as lowering blood glucose vegetable by Indonesian. A. esculentus has a high antioxidant activity that can: 1) lower H2O2 level; 2) decrease the amount of ROS; 3) lower •OH level. This study tried to prove that administration of A. esculentus may decrease fasting blood glucose, serum malondialdehyde, and increase superoxide dismutase activity of diabetic male white rats. This research is a pure experimental research, with randomized post test only control group designs, held in 28 days. Thirty one rats were divided into 4 groups randomly: KN = normal control group given 0.1% Na-CMC solution; KDM = DM control group injected with STZ, followed by 0.1% Na-CMC solution; P1 = treatment group 1 injected with STZ, followed by administration of A. esculentus at a dose of 775 mg/kgBW/day; P2 = treatment group 2 injected with STZ, followed by administration of A. esculentus at a dose of 1550 mg/kgBW/day. The result: administration of A. esculentus at doses of 775 mg/kgBW/day and 1550 mg/kgBW/day can not decrease fasting blood glucose and MDA serum level of diabetic male white rats. Giving A. esculentus at a dose of 1550 mg/kgBW/day may increase the activity of SOD erythrocytes of diabetic male white rats.. Conclusions: A. esculentus has the potential to lower blood glucose and MDA serum levels, also increase erythrocyte SOD activity.


2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Fen Yuan ◽  
Dingkun Wang ◽  
Leyi Ma ◽  
Xin Qin ◽  
Jing Gong ◽  
...  

Huanglian-Renshen-Decoction (HRD) is widely used to treat type 2 diabetes mellitus (T2DM) in China. However, the underlying mechanism is unclear. We aimed to investigate the mechanism by which HRD regulates the glucose level. Forty 7-8-week-old db/db (BSK) mice were randomly assigned to the following four groups: model, low dose HRD (LHRD), high dose HRD (HHRD), and saxagliptin (SAX). Additionally, 10 db/m mice were assigned to control group. The experimental mice were administered 3.03g/kg/d and 6.06g/kg/d of HRD in the LHRD and HHRD groups, respectively, and 10mg/kg/d saxagliptin in the SAX group for 8 weeks. The control and model groups were supplied with distilled water. After the intervention, the pancreas and blood were collected and tested. Compared with that of model group, the fasting blood glucose (FBG) was significantly decreased in all intervention groups (p < 0.05 or 0.01), whereas fasting serum insulin (FINS) was increased significantly in both HHRD and SAX groups. The immunofluorescence images showed that the mass of insulin+ cells was increased and that of glucagon+ cells was reduced obviously in experimental groups compared to those of the model group. In addition, the coexpression of insulin, glucagon, and PDX1 was decreased in HHRD group, and the level of caspase 12 in islet was decreased significantly in all intervention groups. However, little difference was found in the number and morphology of islet, and the expression of ki67, bcl2, bax, caspase 3, and cleaved-caspase 3 in the pancreas among groups. Interestingly, the cleaved-Notch1 level was increased and the Ngn3 level in islet was decreased significantly in HHRD group. The HRD showed dose-dependent effects on glucose metabolism improvement through maintenance of β cell identity via a mechanism that might involve the Notch1/Ngn3 signal pathway in db/db mice.


Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 740-747
Author(s):  
Jiangning Yin ◽  
Jun Jiang ◽  
Huajun Wang ◽  
Guoyuan Lu

AbstractBackgroundWe aim to investigate the protective effects and potential mechanisms in specneuzhenide (SPE) on renal injury in rats with diabetic nephropathy (DN).ResultsSPE could inhibit the decrease of body weight compared with the model group (P<0.05), and trigger improvement in the renal index (P<0.05). High dose and low dose SPE could trigger a significant decrease in serum IL1β, IL-6 and TNF-α compared with the model group (P<0.05). SPE could attenuate the glomerular lesions in DN rats. SPE induced up-regulation of podocin and CD2AP (P<0.05).ConclusionSPE showed protective effects on renal injury through attenuating the pathological injury and urine protein. This process may be closely related to the modulation of CD2AP and podocin expression.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Shanshan Song ◽  
Rui Li ◽  
Bingyan Cao ◽  
Jingyi Zhang ◽  
Youngcho Kim ◽  
...  

Objective. To explore the possible mechanism of electroacupuncture to improve insulin sensitivity in type 2 diabetes rats. Methods. Fourteen Zucker Diabetic Fatty (ZDF) rats were randomly divided into two groups: a model group and an electroacupuncture group, with 7 rats in each group. Seven Zucker Lean (ZL) rats served as a control group. All rats were fed with Purina #5008 for 4 weeks, and the electroacupuncture group received 4-week electroacupuncture intervention, while the control group and model group received no intervention. We measured fasting blood glucose (FBG) on the fourth weekend. After 4 weeks of intervention, the expression levels of insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, IRS-1 serine/threonine phosphorylation, and GLUT4 in quadriceps femoris muscles were detected by western Blot. Results. Compared with the model group, the electroacupuncture group had a lower level of fasting blood glucose, serum insulin level, and insulin resistance index ( P < 0.05 ). The electroacupuncture group had lower IRS-1 serine/threonine phosphorylation than the model group, with the difference showing statistical significance ( P < 0.05 ). Furthermore, the mean score (MS) of the control group showed the lowest phosphorylation expression, followed by the electroacupuncture group, while the model group had the highest level of phosphorylated protein expression. The level of IRS-1 tyrosine phosphorylation at Tyr895 sites was compared, and the result showed that there was no significant difference between the electroacupuncture group and the control group ( P > 0.05 ), and the electroacupuncture group had higher phosphorylation expression than the model group ( P < 0.05 ). Compared with the control group and the model group, the expression level of GLUT4 protein in the electroacupuncture group was significantly increased ( P < 0.05 ). Conclusion. Electroacupuncture has the effect to improve the insulin sensitivity of type 2 diabetic ZDF rats by reducing fasting blood glucose, insulin level, and insulin resistance index, effectively up regulating the expression of GLUT4 protein in quadriceps femoris muscle. The mechanism is related to the regulation of skeletal muscle IRS-1 serine/threonine and tyrosine phosphorylation levels.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Xin Tao ◽  
Lisi Cai ◽  
Lei Chen ◽  
Shuqi Ge ◽  
Xuanying Deng

Abstract Aims This study was designed to evaluate the protective effects of AMPKα and SIRT1 on insulin resistance in PCOS rats, and to illuminate the underlying mechanisms. Methods An in vitro PCOS model was established by DHEA (6 mg/(100 g•d)), and the rats were randomly divided into the metformin group (MF group, n = 11), the exenatide group (EX group, n = 11), the PCOS group (n = 10), and the normal control group (NC group, n = 10). The MF group was administered MF 300 mg/(kg•d) daily. The EX group was subcutaneously injected EX 10μg/(kg•d) daily. After 4 weeks of continuous administration, fasting blood glucose and serum androgen, luteinizing hormone and other biochemical indicators were measured. Western and Real-time PCR were used to determine the expression of AMPKα and SIRT1 in the ovaries of each group. Results After 4 weeks of drug intervention, compared with untreated PCOS group, EX group and MF group had visibly decreased body weight (222.64 ± 16.57, 218.63 ± 13.18 vs 238.30 ± 12.26 g, P = 0.026), fasting blood glucose (7.71 ± 0.72, 8.17 ± 0.54 vs 8.68 ± 0.47 mmol/L, P < 0.01), HOMA-IR (8.26 ± 2.50, 7.44 ± 1.23 vs 12.66 ± 1.44, P < 0.01) and serum androgen (0.09 ± 0.03, 0.09 ± 0.03 vs 0.53 ± 0.41 ng/ml, P < 0.01) and the expressions of AMPKα and SIRT11 were increased progressively (P < 0.05). Conclusions Both metformin and exenatide can improve the reproductive and endocrine functions of rats with PCOS via the AMPKα-SIRT1 pathway, which may be the molecular mechanism for IR in PCOS and could possibly serve as a therapeutic target.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Qian Zhang ◽  
Xinhua Xiao ◽  
Ming Li ◽  
Wenhui Li ◽  
Miao Yu ◽  
...  

In China, TianMai Xiaoke tablet (TM) is used to treat type 2 diabetes. However, the exact mechanism of TM is not clear. This study is to investigate the effect of TM on glucose metabolism in diabetic rats and to identify whether TM takes a direct action through microRNAs on islet. Rats were divided into control group, diabetic group, low dose of TM group (TML), and high dose of TM group (TMH). Pancreas samples were analyzed using microRNA array and Q-PCR. Eight-week treatment with TM significantly decreased fasting blood glucose. The blood glucose was significantly reduced in TM-treated groups before and after oral glucose administration. Fasting insulin and HOMA-IR were suppressed in TM-treated groups. miR-448, let-7b, miR-540, miR-296, miR-880, miR-200a, miR-500, miR-10b, miR-336, miR-30d, miR-208, let-7e, miR-142-5p, miR-874, miR-375, miR-879, miR-501, and miR-188 were upregulated, while miR-301b, miR-134, and miR-652 were downregulated in TMH group. Through target gene analysis and real-time PCR verification, we found that these miRNAs, especially miR-375 and miR-30d, can stimulate insulin secretion in islet. Our data suggest that TM can improve blood glucose in diabetic rats which involved increasing the expression of miR-375 and miR-30d to activate insulin synthesis in islet.


2020 ◽  
Vol 11 (4) ◽  
pp. 5067-5070
Author(s):  
Pang Jyh Chayng ◽  
Nurul Ain ◽  
Kaswandi Md Ambia ◽  
Rahim Md Noah

The purpose of this project is to study the anti-diabetic effect of on a diabetic rat model. A total of Twenty male Sprague rats were used and it randomly distributed into four groups which are Group I: , Group II: negative control, Group III: and Group IV: and . In diabetic model were induced with via injection at the dosage of 65mg/kg. and FBG (Fasting Blood Glucose) level of diabetic rats were assessed every three days. Blood was collected via cardiac puncture at day 21 after the induction of treatment. Insulin level of the rats was assessed with the Mercodia Rat Insulin ELISA kit. FBG level of group I (12.16 ±3.96, p&lt;0.05) and group IV (11.34 ±3.67, p&lt;0.05) were significantly decreased. Meanwhile, the for all rats did not show any significant increase. However, the insulin level was escalated in group IV (0.74+0.25, p&lt;0.05) significantly. The present study shows that the and the combination of and lowered blood glucose level and enhanced insulin secretion.


2018 ◽  
Vol 24 (27) ◽  
pp. 3223-3231 ◽  
Author(s):  
Luyao Li ◽  
Shiyao Xu ◽  
Tingting Guo ◽  
Shouliang Gong ◽  
Chuan Zhang

Objective: To investigate the effect of dapagliflozin on intestinal microflora in MafA-deficient mice using an animal model of diabetes. Methods: Male MafA-deficient mice were administered dapagliflozin (1.0 mg/kg/d) intragastrically for 6 weeks. Mouse body weights and fasting blood glucose levels were measured, and intestinal short-chain fatty acids were measured by gas chromatography. A series of methods was used to analyse the number of primary harmful bacteria in the faeces, and high-throughput sequencing was used to sequence the changes in intestinal flora. Results: The weight of the mice decreased after dapagliflozin gavage, and fasting blood glucose was significantly lower than that in the control group (P < 0.001). Acetic acid and butyric acid contents in the intestinal tracts of the mice increased, and the growth of harmful microorganisms, such as Clostridium perfringens, enterococci, Enterobacteriaceae, and intestinal enterococci, was inhibited. Blautia is a species found in the experimental group and was significantly different from the control and blank groups as determined by the LDA score from highthroughput sequencing. Conclusion: Dapagliflozin can reduce fasting blood glucose, decrease body weight, increase short-chain fatty acid content, regulate the intestinal microecological balance of the body and promote blood glucose and energy homeostasis.


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