scholarly journals Hypolipidaemic and antioxidative effects of oligonol, a low-molecular-weight polyphenol derived from lychee fruit, on renal damage in type 2 diabetic mice

2010 ◽  
Vol 104 (8) ◽  
pp. 1120-1128 ◽  
Author(s):  
Jeong Sook Noh ◽  
Hyun Young Kim ◽  
Chan Hum Park ◽  
Hajime Fujii ◽  
Takako Yokozawa

Oligonol was orally administered at 10 or 20 mg/kg body weight per d for 8 weeks to db/db mice with type 2 diabetes, and its effects were compared with those of the vehicle in db/db and m/m (misty, non-diabetic) mice. Serum and renal biochemical factors, protein expressions related to lipid metabolism and inflammation, and advanced glycation endproducts were measured. There were significant reductions in the serum lipid concentration, reactive oxygen species (ROS) and lipid peroxidation, as well as improvements in renal function parameters. In addition, oligonol treatment significantly decreased ROS levels and lipid peroxidation in the kidney. In particular, the renal lipid contents such as TAG and total cholesterol were significantly reduced in the oligonol-administered groups through the up-regulation of PPARα and down-regulation of sterol regulatory element-binding protein-1 in db/db mice. Moreover, oligonol inhibited non-fluorescent AGE formation and their receptor expression, suggesting that it could effectively inhibit AGE development caused by oxidative stress and/or dyslipidaemia in the kidney of db/db mice. Furthermore, augmented expressions of NF-κBp65, cyclo-oxygenase-2 and inducible NO synthase were down-regulated to the levels of m/m mice in the group given oligonol at 20 mg/kg. This means that oligonol would act as a regulator in the inflammatory response of type 2 diabetes. The present results suggest that oligonol could have renoprotective effects against abnormal lipid metabolism and ROS-related AGE formation in type 2 diabetes.

2011 ◽  
Vol 106 (7) ◽  
pp. 1013-1022 ◽  
Author(s):  
Jeong Sook Noh ◽  
Chan Hum Park ◽  
Takako Yokozawa

We have identified the effects of oligonol, a low-molecular polyphenol derived from lychee fruit, on oxidative stress and lipid metabolism in a type 2 diabetic model. Oligonol was orally administered at 10 or 20 mg per kg body weight per d for 8 weeks to db/db mice, and its effects were compared with those of the vehicle in db/db and m/m mice. Serum and hepatic biochemical factors, and protein and mRNA expression related to lipid metabolism were measured. In the oligonol-administered group, there were significant reductions of reactive oxygen species (ROS), lipid peroxidation, and the TAG and total cholesterol concentrations in both the serum and liver. Additionally, oligonol attenuated oxidative stress through the inhibition of advanced glycation endproduct formation and its receptor expression. Furthermore, augmented expressions of NF-κBp65 and inducible NO synthase were down-regulated to the levels of m/m mice in the group treated with oligonol at 20 mg/kg. Regarding lipid metabolism, lower hepatic lipid resulted from the down-regulation of sterol regulatory element-binding protein-1 and its target gene of lipogenic enzymes in the liver of db/db mice. The present results suggest that oligonol has protective effects against ROS-related inflammation and excess lipid deposition in the type 2 diabetic liver.


Endocrinology ◽  
2009 ◽  
Vol 150 (6) ◽  
pp. 2611-2617 ◽  
Author(s):  
Betty C. Villafuerte ◽  
Michelle T. Barati ◽  
Ying Song ◽  
Joseph P. Moore ◽  
Paul N. Epstein ◽  
...  

Recent evidence supports the idea that insulin signaling through the insulin receptor substrate/phosphatidyl-inositol 3-kinase/Akt pathway is involved in the maintenance of β-cell mass and function. We previously identified the insulin-response element binding protein-1 (IRE-BP1) as an effector of insulin-induced Akt signaling in the liver, and showed that the 50-kDa carboxyl fragment confers the transcriptional activity of this factor. In this investigation we found that IRE-BP1 is expressed in the α, β, and δ-cells of the islets of Langerhans, and is localized to the cytoplasm in β-cells in normal rats, but is reduced and redistributed to the islet cell nuclei in obese Zucker rats. To test whether IRE-BP1 modulates β-cell function and insulin secretion, we used the rat insulin II promoter to drive expression of the carboxyl fragment in β-cells. Transgenic expression of IRE-BP1 in FVB mice increases nuclear IRE-BP1 expression, and produces a phenotype similar to that of type 2 diabetes, with hyperinsulinemia, hyperglycemia, and increased body weight. IRE-BP1 increased islet type I IGF receptor expression, potentially contributing to the development of islet hypertrophy. Our findings suggest that increased gene transcription mediated through IRE-BP1 may contribute to β-cell dysfunction in insulin resistance, and allow for the hypothesis that IRE-BP1 plays a role in the pathophysiology of type 2 diabetes.


2009 ◽  
Vol 29 (5) ◽  
pp. 283-292 ◽  
Author(s):  
Ali Ben Djoudi Ouadda ◽  
Emile Levy ◽  
Ehud Ziv ◽  
Geneviève Lalonde ◽  
Alain T. Sané ◽  
...  

AMPK (AMP-activated protein kinase) has been suggested to be a central player regulating FA (fatty acid) metabolism through its ability to regulate ACC (acetyl-CoA carboxylase) activity. Nevertheless, its involvement in insulin resistance- and TD2 (Type 2 diabetes)-associated dyslipidaemia remains enigmatic. In the present study, we employed the Psammomys obesus gerbil, a well-established model of insulin resistance and TD2, in order to appreciate the contribution of the AMPK/ACC pathway to the abnormal hepatic lipid synthesis and increased lipid accumulation in the liver. Our investigation provided evidence that the development of insulin resistance/diabetic state in P. obesus is accompanied by (i) body weight gain and hyperlipidaemia; (ii) elevations of hepatic ACC-Ser79 phosphorylation and ACC protein levels; (iii) a rise in the gene expression of cytosolic ACC1 concomitant with invariable mitochondrial ACC2; (iv) an increase in hepatic AMPKα-Thr172 phosphorylation and protein expression without any modification in the calculated ratio of phospho-AMPKα to total AMPKα; (v) a stimulation in ACC activity despite increased AMPKα phosphorylation and protein expression; and (vi) a trend of increase in mRNA levels of key lipogenic enzymes [SCD-1 (stearoyl-CoA desaturase-1), mGPAT (mitochondrial isoform of glycerol-3-phosphate acyltransferase) and FAS (FA synthase)] and transcription factors [SREBP-1 (sterol-regulatory-element-binding protein-1) and ChREBP (carbohydrate responsive element-binding protein)]. Altogether, our findings suggest that up-regulation of the AMPK pathway seems to be a natural response in order to reduce lipid metabolism abnormalities, thus supporting the role of AMPK as a promising target for the treatment of TD2-associated dyslipidaemia.


2021 ◽  
Vol 71 (4) ◽  
pp. 1126-29
Author(s):  
Ejaz Ali ◽  
Abdul Latif Khattak ◽  
Andaleeb Khan ◽  
Kamil Rehman Butt ◽  
Raheel Akhtar Yousafzai ◽  
...  

Objective: To determine the frequency of dyslipidaemia in type-2 diabetic patients and to compare the frequency of dyslipidaemia in patients with and without microalbuminuria in type 2 diabetes. Study Design: cross-sectional study. Place and Duration of Study: Department of General Medicine, Combined Military Hospital Quetta Pakistan, from Dec 2018 to Jun 2019. Methodology: All patients who fulfilled the inclusion criteria and visited General Medicine department of Combined Military Hospital Quetta with type II diabetes mellitus were included in the study. Blood sample following an 8-12 hours fasting over the last night and 24 hour urine sample for microalbuminuria was collected to assess the outcome i.e. frequency of dyslipidaemia and also its frequency with and without microalbuminuria. Result: A total of 165 patients with type 2 diabetes mellitus were included. Ninety nine (60%) were males and 66 (40%) were females with the mean age of 48.08 ± 7.63 years. Overall, dyslipidaemia was found in 48 (29.1%) patients, dyslipidaemia was noted in 29 (17.6%) with microalbuminuria and 19 (11.5%) without microalbuminuria. Chi-square test revealed that dyslipidaemia was significantly more in patients of diabetes mellites having microalbuminuria than those not having it (p-value=0.01). Conclusion: Abnormal lipid metabolism was present in significantly more in patients with microalbuminuria as compared to those without microalbuminuria suffering from type II diabetes mellitus.


Author(s):  
K.A. Cherepanova

Objective. The aim of the paper is to analyze the impact of plant antioxidant “Dihydroquercetin Baikalsky” on the LPO-AOS system and carbohydrate-lipid metabolism in residents of Khanty-Mansiysk with type 2 diabetes mellitus. Materials and Methods. The study enrolled 132 adult residents of Khanty-Mansiysk, including 78 people with type 2 diabetes mellitus and 54 healthy subjects. The authors examined the indicators of pro- and antioxidant activity in blood samples in all the trial subjects: products of lipid peroxidation (LPO), the state of the antioxidant system (AOS), oxidative stress coefficient. Patients with type 2 diabetes mellitus (n=48) undergoing standard glucose-lowering therapy were taking 1 capsule (60 mg) of Dihydroquercetin Baikalsky post cibum daily. Statistica 10.0 and Microsoft Excel software package were used to process the results obtained. Results. It was found that 12-week dihydroquercetin intake led to a significant decrease in primary and secondary lipid peroxidation products and an increase of AOS activity, which indicated the antioxidant effect of the bioflavonoid. The authors noted a positive trend towards a decrease in the parameters of the carbohydrate-lipid profile. Conclusion. The data obtained indicate the antioxidant properties of dihydroquercetin in persons with type 2 diabetes mellitus. Keywords: northern region, lipid peroxidation, antioxidant system, carbohydrate-lipid metabolism, dihydroquercetin. Цель. Провести анализ коррекции показателей системы ПОЛ – АОС и углеводно-липидного обмена антиоксидантом растительного происхождения «Дигидрокверцетин Байкальский» у жителей г. Ханты-Мансийск, страдающих сахарным диабетом 2 типа. Материалы и методы. В исследование включены 132 взрослых жителя г. Ханты-Мансийск, в т.ч. 78 чел. с сахарным диабетом 2 типа и 54 условно здоровых добровольца. У обследуемых лиц изучены показатели про- и антиоксидантной активности в образцах крови: продукты перекисного окисления липидов (ПОЛ), состояние антиоксидантной системы (АОС), коэффициент окислительного стресса. Группа больных сахарным диабетом 2 типа (48 чел.) на фоне стандартной сахароснижающей терапии в течение 12 нед. принимала после еды по 1 капсуле (60 мг) в день антиоксиданта «Дигидрокверцетин Байкальский». Полученные результаты статистически обработаны с использованием пакета программ Statistica 10.0 и Microsoft Excel. Результаты. Установлено, что прием дигидрокверцетина в течение 12 нед. способствовал достоверному снижению содержания первичных и вторичных продуктов ПОЛ и повышению активности АОС, что свидетельствует об антиоксидантном действии данного биофлавоноида. Отмечена положительная тенденция к снижению показателей углеводно-липидного профиля. Выводы. Полученные данные указывают на антиокислительные свойства дигидрокверцетина у лиц, страдающих сахарным диабетом 2 типа. Ключевые слова: северный регион, перекисное окисление липидов, антиоксидантная система, углеводно-липидный обмен, дигидрокверцетин.


2018 ◽  
Vol 9 (7) ◽  
pp. 3630-3639 ◽  
Author(s):  
Fangfang Dang ◽  
Yujun Jiang ◽  
Ruili Pan ◽  
Yanhong Zhou ◽  
Shuang Wu ◽  
...  

Lactobacillus paracasei TD062 with high inhibitory activity ameliorated lipid metabolism, oxidative stress, glucose metabolism and the PI3K/Akt pathway in diabetic mice, and the effects were dose-dependent to some extent.


2019 ◽  
Author(s):  
DaoFei Song ◽  
Lei Yin ◽  
Chang Wang ◽  
XiuYing Wen

AbstractAIMIn this study, we investigated the role and mechanism of Salt-induced kinase 1 (SIK1) in regulation of hepatic glucose and lipid metabolism in a high-fat food (HFD) and streptozocin (STZ)-induced type 2 diabetes mellitus (T2DM) rat model.MethodsA diabetic rat model treated with HFD plus low-dose STZ was developed and was transduced to induce a high expression of SIK1 in vivo via a tail-vein injection of a recombinant adenoviral vector. The effects on hepatic glucogenetic and lipogenic gene expression, systemic metabolism and pathological changes were then determined.ResultsIn T2DM rats, SIK1 expression was reduced in the liver. Overexpression of SIK1 improved hyperglycaemia, hyperlipidaemia and fatty liver, reduced the expression of cAMP-response element binding protein (CREB)-regulated transcription co-activator 2 (CRTC2), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), pS577 SIK1, sterol regulatory element binding-protein-1c (SREBP-1c) and its target genes, including acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), and increased the expression of SIK1, pT182 SIK1 and pS171 CRTC2 in diabetic rat livers with the suppression of gluconeogenesis and lipid deposition.ConclusionSIK1 plays a crucial role in the regulation of glucose and lipid metabolism in the livers of HFD/STZ-induced T2DM rats, where it suppresses hepatic gluconeogenesis and lipogenesis by regulating the SIK1/CRTC2 and SIK1/SREBP-1c signalling pathways. Strategies to activate SIK1 kinase in liver would likely have beneficial effects in patients with T2DM and nonalcoholic fatty liver disease (NAFLD).


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