scholarly journals Retinoprotection by BGP-15, a Hydroximic Acid Derivative, in a Type II Diabetic Rat Model Compared to Glibenclamide, Metformin, and Pioglitazone

2020 ◽  
Vol 21 (6) ◽  
pp. 2124 ◽  
Author(s):  
Zita Wachal ◽  
Mariann Bombicz ◽  
Dániel Priksz ◽  
Csaba Hegedűs ◽  
Diána Kovács ◽  
...  

High blood glucose and the consequential ischemia-reperfusion (I/R) injury damage vessels of the retina, deteriorating its function, which can be clearly visualized by electroretinography (ERG). The aim of the present study was to evaluate the possible retinoprotective effects of systemic BGP-15, an emerging drug candidate, in an insulin resistant animal model, the Goto-Kakizaki rat, and compare these results with well-known anti-diabetics such as glibenclamide, metformin, and pioglitazone, which even led to some novel conclusions about these well-known agents. Experiments were carried out on diseased animal model (Goto-Kakizaki rats). The used methods include weight measurement, glucose-related measurements—like fasting blood sugar analysis, oral glucose tolerance test, hyperinsulinemic euglycemic glucose clamp (HEGC), and calculations of different indices from HEGC results—electroretinography and Western Blot. Beside its apparent insulin sensitization, BGP-15 was also able to counteract the retina-damaging effect of Type II diabetes comparable to the aforementioned anti-diabetics. The mechanism of retinoprotective action may include sirtuin 1 (SIRT1) and matrix metalloproteinase 9 (MMP9) enzymes, as BGP-15 was able to elevate SIRT1 and decrease MMP9 expression in the eye. Based on our results, this emerging hydroximic acid derivative might be a future target of pharmacological developments as a potential drug against the harmful consequences of diabetes, such as diabetic retinopathy.

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jai Sun Lee ◽  
Dae Won Jun ◽  
Eun Kyung Kim ◽  
Hye Joon Jeon ◽  
Ho Hyun Nam ◽  
...  

Background. We used high-fat (HF), high-fructose (HFr), and combination diets to create a dietary animal model of nonalcoholic fatty liver disease (NAFLD). Comparison of both clinical phenotypes has not been well defined. The purpose of this study was to compare histologic and metabolic characteristics between diets in an animal model of NAFLD.Methods. NAFLD was induced in rats by feeding them HF, HFr, and combination (HF + HFr) diets for 20 weeks. The degree of intrahepatic fat accumulation, inflammation, and oxidative stress was evaluated. Metabolic derangements were assessed by the oral glucose tolerance test and the intrahepatic insulin signal pathway.Results. Body weight gain and intrahepatic fat accumulation were more prominent in the HF feeding group than in the HFr group. The expressions of NOX-4 and TLR-4 were higher in the HF and HFr combination groups than in the HF-only group. Other intrahepatic inflammatory markers, MCP-1, TNF-α, and endoplasmic reticulum stress markers, were the highest in the HF + HFr combination group. Although intrahepatic fat deposition was less prominent in the HFr diet model, intrahepatic inflammation was noted.Conclusions. Intrahepatic inflammation and metabolic derangements were more prominent in the HF and HFr combination model than in the HF monodiet model.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Maria Alexandra Bernardo ◽  
Maria Leonor Silva ◽  
Elisabeth Santos ◽  
Margarida Maria Moncada ◽  
José Brito ◽  
...  

Glycaemic control, in particular at postprandial period, has a key role in prevention of different diseases, including diabetes and cardiovascular events. Previous studies suggest that postprandial high blood glucose levels (BGL) can lead to an oxidative stress status, which is associated with metabolic alterations. Cinnamon powder has demonstrated a beneficial effect on postprandial glucose homeostasis in animals and human models. The purpose of this study is to investigate the effect of cinnamon tea (C. burmannii) on postprandial capillary blood glucose level on nondiabetic adults. Participants were given oral glucose tolerance test either with or without cinnamon tea in a randomized clinical trial. The data revealed that cinnamon tea administration slightly decreased postprandial BGL. Cinnamon tea ingestion also results in a significantly lower postprandial maximum glucose concentration and variation of maximum glucose concentration (p< 0.05). Chemical analysis showed that cinnamon tea has a high antioxidant capacity, which may be due to its polyphenol content. The present study provides evidence that cinnamon tea, obtained fromC. burmannii, could be beneficial for controlling glucose metabolism in nondiabetic adults during postprandial period.


2011 ◽  
Vol 57 (5) ◽  
pp. 490-500 ◽  
Author(s):  
J. Sokolovska ◽  
J. Rumaks ◽  
N. Karajeva ◽  
D. Grinvalde ◽  
J. Sharipova ◽  
...  

Streptozotocin (STZ) was used to induce the diabetic rat model. STZ rats were treated with mildronate (100 mg/kg daily, per os or intraperitoneally for 6 weeks). Body weight, blood glucose, triglyceride, ketone body concentrations, glycated hemoglobin percent (HbA1c%), glucose tolerance, and the development of neuropathic pain were monitored throughout the experiment. In the STZ + mildronate group, mildronate treatment caused a significant decrease in mean blood glucose (on week 4) and triglyceride concentrations (on weeks 3-6), significantly slowed the increase in HbA1c% (on week 6) and improved glucose tolerance 120 minutes after glucose ingestion during oral glucose tolerance test versus the STZ group. Mildronate completely protected development of STZ-induced neuropathic pain from the first administration week up to end of the experiment. The obtained data indicate clinical usefulness of the drug for the treatment of diabetes mellitus and its complications.


Author(s):  
Fadwa El-Ouady ◽  
Nadia Lahrach ◽  
Mohammed Ajebli ◽  
Ahmed E. Haidani ◽  
Mohamed Eddouks

Background: Diabetes mellitus is associated with high blood glucose levels due to insulin shortcoming (insulinopenia) or defective insulin action. The objective of the study was to investigate the antidiabetic and antioxidant effects of Foeniculum vulgare in streptozotocin-induced diabetic rat. Methods: The effects of the leaves aqueous extract (LAE) of Foeniculum vulgare (F. vulgare) at a dose of 10 mg/kg on blood glucose levels were evaluated in normal and streptozotocin (STZ)- induced diabetic rats. Histopathological changes were also evaluated in liver in STZ-induced rats. Results: Single oral administration of F. vulgare LAE reduced blood glucose levels 6 h after administration in STZ diabetic rats (p<0.0001). Furthermore, blood glucose levels were decreased in both normal (p<0.05) and STZ diabetic rats (p<0.0001) after the fifteenth day of treatment. During this test, both groups did not show any significant change in their body weight. Moreover, this aqueous extract improved oral glucose tolerance in diabetic rats and revealed a positive effect on liver histology. On the other hand, the extract used in this experiment showed an inhibitory concentration (IC50) of 50% of free radicals with a concentration of 43±1.19 µg/ml. While the synthetic antioxidant (BHT) had an IC50 equal to 22.67±2.17µg /ml. Conclusion: This study demonstrates the antihyperglycemic, hypoglycemic and antioxidant effects of the leaves of F. vulgare in normal and diabetic rats.


2007 ◽  
Vol 23 (9) ◽  
pp. 2145-2156 ◽  
Author(s):  
Flavia Cincotto Massimino ◽  
Suely Godoy Agostinho Gimeno ◽  
Sandra Roberta Gouveia Ferreira

The aim of this study was to verify the association between nutritional variables and mortality in a Japanese-Brazilian cohort. In 1993, 647 subjects were interviewed with food frequency questionnaires and scheduled for physical procedures (weight, height, blood pressure) and biochemical tests (oral glucose tolerance test). Student's t test was used to compare the mean values of target variables between living and deceased subjects. Mortality rate and hazard ratios were obtained (crude and adjusted) according to the nutritional variables. Overall mortality rates were 21.4 and 11.7/1,000 person-years for males and females, respectively. Smoking, diabetes, sedentary lifestyle, hypertension, higher mean age, high blood pressure, high blood glucose, and higher percent weight gain and rate of weight gain were observed in the history of deceased subjects. After adjusting for control variables, an increase was observed in mortality among individuals with lower carbohydrate and cholesterol intake. The results suggest that mortality risk factors like age, chronic diseases, sedentary lifestyle, smoking, and inadequate diet must also be acting in the Japanese-Brazilian population.


2017 ◽  
Vol 232 (3) ◽  
pp. 501-511 ◽  
Author(s):  
Guillermo Vazquez-Anaya ◽  
Bridget Martinez ◽  
José G Soñanez-Organis ◽  
Daisuke Nakano ◽  
Akira Nishiyama ◽  
...  

Both hypothyroidism and hyperthyroidism are associated with glucose intolerance, calling into question the contribution of thyroid hormones (TH) on glucose regulation. TH analogues and derivatives may be effective treatment options for glucose intolerance and insulin resistance (IR), but their potential glucoregulatory effects during conditions of impaired metabolism are not well described. To assess the effects of thyroxine (T4) on glucose intolerance in a model of insulin resistance, an oral glucose tolerance test (oGTT) was performed on three groups of rats (n = 8): (1) lean, Long Evans Tokushima Otsuka (LETO), (2) obese, Otsuka Long Evans Tokushima Fatty (OLETF) and (3) OLETF + T4 (8.0 µg/100 g BM/day × 5 weeks). T4 attenuated glucose intolerance by 15% and decreased IR index (IRI) by 34% in T4-treated OLETF compared to untreated OLETF despite a 31% decrease in muscle Glut4 mRNA expression. T4 increased the mRNA expressions of muscle monocarboxylate transporter 10 (Mct10), deiodinase type 2 (Di2), sirtuin 1 (Sirt1) and uncoupling protein 2 (Ucp2) by 1.8-, 2.2-, 2.7- and 1.4-fold, respectively, compared to OLETF. Activation of AMP-activated protein kinase (AMPK) and insulin receptor were not significantly altered suggesting that the improvements in glucose intolerance and IR were independent of enhanced insulin-mediated signaling. The results suggest that T4 treatment increased the influx of T4 in skeletal muscle and, with an increase of DI2, increased the availability of the biologically active T3 to upregulate key factors such SIRT1 and UCP2 involved in cellular metabolism and glucose homeostasis.


Author(s):  
Yang Yang ◽  
Man-Xia Lu ◽  
Qin-Peng Zou ◽  
Xiang-Qian Liu ◽  
Eun-Hee Hwang

This present study was designed to find out whether the acankoreagenin showed the antidiabetic and renoprotective effects in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats. Type I diabetes was induced by a single intraperitoneal injection of STZ (70 mg/kg). At the end of the experiment, rats were euthanized and serum/plasma was separated for the determination of glucose, insulin, glycated hemoglobin A1c (HbA1c), C-peptide, biochemical parameters, and kidney function. One kidney was used for determining glutathione, superoxide dismutas, malondialdehyde, and tumor necrosis factor-alpha levels. The other kidney and pancreas were used for histopathological studies and immunohistochemical measurement of transforming growth factor beta (TGF-&beta;) or NF-&kappa;B. Acankoreagenin (2 mg/kg) treatments led to a significant reduction in blood glucose assessed via oral glucose tolerance test (OGTT) in diabetic rats at 2 h. The treatment also resulted in improved body weight, decreased HbA1c, restored lipid profile, and renal oxidative stress. By inhibiting NF-&kappa;B, the release of proinflammatory cytokines was suppressed and by inhibiting TGF-&beta;, the renal fibrosis was suppressed in STZ-induced diabetic rat model. Histopathological injury was also observed in pancreatic and renal tissues. These findings support the beneficial effect of acankoreagenin treatment in DN, which could be attributed to its antidiabetic and renoprotective effects.


2020 ◽  
Vol 10 (3) ◽  
pp. 226-235
Author(s):  
Nisha H. Parikh ◽  
Charmy Kothari

Background: Ocimum basilicum seed, commonly also known as Takhmaria in Gujarat. The seed of O. basilicum traditionally used to treat diabetes. This activity is related to the presence of flavonoids, the major compounds of the crude extract. Objective: The present study was planned to examine the antidiabetic and antihyperlipidemic potential of Ocimum basilicum Linn seed, used as a traditional treatment for diabetes mellitus. Methods: The methanolic extracts of O. basilicum seed (40 mg/kg) and isolated compound apigenin (10 mg/kg) were administered orally for 15 days to streptozotocin (STZ)-induced diabetic rat. Anti diabetic activity, oral glucose tolerance test, change in body weight and lipid profile of diabetics rat treated with methanolic extracts of O. basilicum seed and isolated apigenin were assessed and which was further compared with normal, diabetic control and standard drug-treated rat. Histological examination was carried out on 15 days of treatment. Results: Methanolic extract of O. basilicum seed (40 mg/kg) and apigenin (10 mg/kg) produced a significant reduction in fasting blood glucose level (p<0.01) and (p<0.001) respectively in the streptozotocin-induced diabetic rat. Significant differences were observed in oral glucose tolerance test, serum lipid parameters and body weight for methanolic extract of O. basilicum and apigenintreated diabetic rat as compared to diabetic, normal and standard drug-treated rat. The outcome of the histological examinations of the pancreas treated with a methanolic extract of O. basilicum and apigenin showed comparable regeneration of the cells, which were earlier necrosed by streptozotocin. Methanolic extract of O. basilicum and isolated compound apigenin exhibit significant antihyperglycemic and antihyperlipidemic activities in streptozotocin-induced diabetes in the rat. Conclusion: From above findings, it can be concluded that the O. basilicum seed and isolated compound apigenin must be considered as a potential candidate for the treatment of diabetes and lipidlowering activities in streptozotocin-induced diabetes in the rat.


Author(s):  
Omar Farid ◽  
Morad Hebi ◽  
Mohammed Ajebli ◽  
Ahmed EL Hidani ◽  
Mohamed Eddouks

AbstractBackground:(L.) is known as a medicinal plant with many beneficial effects, including those that can be used in the treatment of diabetes. The objective of the study was to investigate the antidiabetic effect of this plant in diabetic rat.Methods:This study investigated the effects of an aerial part aqueous extract (APAE) ofResults:Both single and repeated oral doses of APAE (5 mg/kg) produced significant reductions in the blood glucose levels in normal and STZ-induced rats. Oral glucose tolerance test results showed that, after the administration of 3 g/kg of glucose, RM APAE (5 mg/kg) improved the increase in blood glucose levels in normal rats at the 30th min (p<0.01) and 90th min (p<0.001).Conclusions:RM APAE exhibits a potent hypoglycemic effect in normal rats and an antidiabetic effect in STZ-induced rats. This finding supports the use of this plant in traditional Moroccan medicine for diabetes management.


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