Glimepiride Loaded Poly(D,L-lactide-co-glycolide) Microspheres Improve Osseointegration of Dental Implants in Type 2 Diabetic Rats

2022 ◽  
Vol 12 (4) ◽  
pp. 756-762
Author(s):  
Changying Liu ◽  
Xuezhu Wei ◽  
Jun Li ◽  
Chao Liang ◽  
Wei Geng ◽  
...  

The patients with type 2 diabetes mellitus (T2DM) have high dental implant failure frequency. This study explores the function of glimepiride local delivery on dental implant osseointegration in diabetes animal. Glimepiride loaded PLGA microspheres were loaded on the surface of the dental implant, and transplanted into ten Goto-Kakizaki (GK) rats. Blood sugar level and Implant Stability Quotient (ISQ) were measured every week after surgery. Histological, osseointegration rate and bone-implant contact (BIC) rate analysis were performed to evaluate dental osseointegration. The results showed that Glimepiride loaded Poly-lactide-co-glycolide (PLGA) microspheres have sustained-release curve. The glimepiride group exhibited greater ISQ than the control group. The BIC rate of the control and glimepiride group was 44.60%±1.95% and 59.80%±1.79%, respectively. This study demonstrated that the glimepiride group has a significantly greater osseointegration rate than that of the control group. Thus, Glimepiride could provide an alternative drug release microspheres for enhance the dental implant osseointegration in diabetes patients.

2020 ◽  
Vol 20 (7) ◽  
pp. 1117-1132
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Ismaeel Bin-Jaliah ◽  
Medhat Taha ◽  
Lashin S. Lashin

Background and Aims: In the current work, we studied the effects of exercise and stevia rebaudiana (R) extracts on diabetic cardiomyopathy (DCM) in type 2 diabetic rats and their possible underlying mechanisms. Methods: : Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group, b) DM group, type 2 diabetic rats received 2 ml oral saline daily for 4 weeks, c) DM+ Exercise, type 2 diabetic rats were treated with exercise for 4 weeks and d) DM+ stevia R extracts: type 2 diabetic rats received methanolic stevia R extracts. By the end of the experiment, serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB), cardiac histopathology, oxidative stress markers (MDA, GSH and CAT), myocardial fibrosis by Masson trichrome, the expression of p53, caspase-3, α-SMA and tyrosine hydroxylase (TH) by immunostaining in myocardial tissues were measured. Results: T2DM caused a significant increase in blood glucose, HOMA-IR index, serum CK-MB and LDH, myocardial damage and fibrosis, myocardial MDA, myocardial α-SMA, p53, caspase-3, Nrf2 and TH density with a significant decrease in serum insulin and myocardial GSH and CAT (p< 0.05). On the other hand, treatment with either exercise or stevia R extracts significantly improved all studied parameters (p< 0.05). Moreover, the effects of stevia R was more significant than exercise (p< 0.05). Conclusion: Both exercise and methanolic stevia R extracts showed cardioprotective effects against DCM and Stevia R offered more cardioprotective than exercise. This cardioprotective effect of these lines of treatment might be due to attenuation of oxidative stress, apoptosis, sympathetic nerve density and fibrosis and upregulation of the antioxidant transcription factor, Nrf2.


2010 ◽  
Vol 38 (04) ◽  
pp. 713-725 ◽  
Author(s):  
Yun-Xia Lu ◽  
Qiu Zhang ◽  
Jun Li ◽  
Yu-Xiu Sun ◽  
Ling-Yun Wang ◽  
...  

This study was initiated to determine the possible antidiabetic effects of total flavonoids of Litsea Coreana leve (TFLC), an alcohol extract from the dried leaves of Litsea Coreana leve, on type 2 diabetic rats. Male Sprague-Dawley rats ( n = 40, 160–180 g) were divided into two groups and fed with normal chow diet (Normal Control group) or high-fat diet (HFD) for a period of 4 weeks. After 4 weeks of dietary manipulation, the HFD-fed rats were injected with 30 mg/kg streptozocin (STZ) to induce diabetes 72 hours after STZ injection. These diabetic rats were randomly divided into 3 groups ( n = 10): Diabetic Control group, Diabetic + TFLC group and Diabetic + PIO group. Diabetic + TFLC group and Diabetic + PIO group were orally administered with 400 mg/kg TFLC or 10 mg/kg pioglitazone (all suspended in 0.5% CMC-Na) respectively for 6 weeks. All rats were examined for body weight, serum and hepatic biochemical indices, content of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and pathological changes in liver and pancreas, as well as protein tyrosine phosphatase 1B (PTP1B) expression in liver. The diabetic rats became obese, insulin resistant, hyperglycemic and hyperlipidemic. Treatment with TFLC showed a significant increase in insulin sensitivity, serum HDL-C level and SOD activities, meanwhile marked decrease in body weight, serum FFA, TC, TG, LDL-C, CRP, MDA content. TFLC also attenuated pathologic alterations in liver and pancreatic islet. Furthermore, TFLC was found to decrease the expression of PTP1B in diabetic rat liver. These results suggested that TFLC could ameliorate hyperglycemia, hyperlipoidemia, inflammation and oxidation stress, as well as insulin resistance of type 2 diabetic rats.


2012 ◽  
Vol 40 (04) ◽  
pp. 721-733 ◽  
Author(s):  
Wenfan Huang ◽  
Jie Yu ◽  
Xuming Jia ◽  
Liang Xiong ◽  
Ningxu Li ◽  
...  

Forkhead box O1 (FOXO1) plays an important role in glucose metabolism at the gene transcription level. Increased FOXO1 activity results in hyperglycemia by promoting the expression of gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), and inhibiting glucokinase (GK). This study evaluates the effect of Zhenqing Recipe (ZQR), a Chinese herbal medicine, on hyperglycemia and its molecular mechanisms. Type 2 diabetic rats, developed by high-fat diet combined with low-dose STZ injections, were randomly divided into untreated diabetic, ZQR and metformin group. Normal rats served as control. After an eight-week treatment, fasting blood glucose was significantly decreased and insulin sensitivity index was obviously increased in the ZQR group. ZQR also improved the oral glucose tolerance. Compared with the control group, the mRNA levels of PEPCK and G6Pase were significantly elevated, while GK mRNA expression was decreased in the liver of untreated diabetic rats. ZQR significantly reduced the mRNA levels of PEPCK and G6Pase, and increased GK mRNA expression. The hepatic mRNA and protein expression of FOXO1 in the untreated diabetic group was markedly increased compared to controls. The administration of ZQR significantly decreased the mRNA and protein levels of hepatic FOXO1. The data suggest that ZQR improves glucose metabolism and insulin sensitivity, which is accompanied with regulating mRNA expression of GK and gluconeogenic genes. This anti-diabetic effect of ZQR is due to its ability to repress hepatic FOXO1 at the mRNA and protein level.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Li-ping Han ◽  
Chun-jun Li ◽  
Bei Sun ◽  
Yun Xie ◽  
Yue Guan ◽  
...  

Immune and inflammatory pathways play a central role in the pathogenesis of diabetic liver injury. Celastrol is a potent immunosuppressive and anti-inflammatory agent. So far, there is no evidence regarding the mechanism of innate immune alterations of celastrol on diabetic liver injury in type 2 diabetic animal models. The present study was aimed at investigating protective effects of celastrol on the liver injury in diabetic rats and at elucidating the possible involved mechanisms. We analyzed the liver histopathological and biochemical changes and the expressions of TLR4 mediated signaling pathway. Compared to the normal control group, diabetic rats were found to have obvious steatohepatitis and proinflammatory cytokine activities were significantly upregulated. Celastrol-treated diabetic rats show reduced hepatic inflammation and macrophages infiltration. The expressions of TLR4, MyD88, NF-κB, and downstream inflammatory factors IL-1βand TNFαin the hepatic tissue of treated rats were downregulated in a dose-dependent manner. We firstly found that celastrol treatment could delay the progression of diabetic liver disease in type 2 diabetic rats via inhibition of TLR4/MyD88/NF-κB signaling cascade pathways and its downstream inflammatory effectors.


2020 ◽  
Vol 16 (1) ◽  
pp. 68
Author(s):  
Ismawati Ismawati ◽  
Ilhami Romus ◽  
Dhea Ayu Kartini Surya Putri

Kelainan pulau Langerhans (isletopathy) merupakan salah satu komplikasi DM tipe 2. Penelitian mengenai  efek asam alfa lipoat (ALA) terhadap matriks ekstraseluler pankreas (ECM) pada DM tipe 2 masih  terbatas. Penelitian ini bertujuan untuk mengetahui efek ALA terhadap ketebalan kolagen ECM sel β pankreas pada tikus diabetes melitus tipe 2. Penelitian eksperimental dengan design post test only control group design  ini menggunakan 15 ekor tikus Rattus novergicus galur Wistar jantan yang dibagi menjadi tiga kelompok, yaitu kelompok kontrol, kelompok diabetes melitus tipe 2, dan kelompok diabetes melitus tipe 2 yang diberi ALA. Induksi diabetes melitus tipe 2 dilakukan dengan pemberian streptozotosin (50 mg/kgBB) diikuti nikotinamid (110 mg/kgBB) intraperitoneal. Dosis ALA yang digunakan 60 mg/kgBB/hari diberikan selama 3 minggu. Ketebalan kolagen matriks ekstraseluler sel β pankreas dinilai dengan pewarnaan Verhoeff's van Gieson (VvG) dengan sistem skoring. Hasil penelitian menunjukkan ketebalan kolagen matriks ekstraseluler pulau Langerhans pankreas tetap normal pada semua kelompok penelitian. Pemberian ALA 60 mg/kgbb selama 3 minggu pada tikus DM tipe 2 tidak memiliki efek terhadap ketebalan kolagen ECM pankreas. Dengan demikian perlu dilakukan penelitian lanjutan mengenai efek ALA terhadap kolagen matriks ekstra seluler pankreas DM tipe 2 tahap lanjut.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Lishan Zhou ◽  
Hui Dong ◽  
Yi Huang ◽  
Lijun Xu ◽  
Xin Zou ◽  
...  

Hu-Lu-Ba-Wan (HLBW) is a Chinese herbal prescription used to treat kidney deficiency. The aim of this study was to explore the effect and mechanism of HLBW on diabetic nephropathy (DN) in type 2 diabetic rats. The rat model of DN was established by being fed a high-fat diet and intravenous injection of streptozotocin. Then, HLBW decoction was administered for 16 weeks. Blood glucose level, lipid profile, renal function, 24-hour total urinary protein, and albumin content were examined. Renal morphology and superoxide anion levels were evaluated. The activity of nicotinamide-adenine dinucleotide phosphate (NADPH) and protein kinase C-alpha (PKC-α) related genes expression in renal tissue were also determined. Our data demonstrated that HLBW significantly improved hyperglycemia, hyperlipidemia, and proteinuria in diabetic rats compared with those of control group. HLBW also alleviated glomerular expansion and fibrosis, extracellular matrix accumulation and effacement of the foot processes. Additionally, HLBW reduced superoxide anion level, NADPH oxidase activity, the protein and mRNA expressions of p47phox, and the protein expression of phosphorylated PKC-αin renal tissue. These results suggest that HLBW is effective in the treatment of DN in rats. The underlying mechanism may be related to the attenuation of renal oxidative stress via PKC-α/NADPH oxidase signaling pathway.


Author(s):  
Sonchita R. Mudi ◽  
Masfida Akhter ◽  
Subrata K. Biswas ◽  
Mohammad A. Muttalib ◽  
Subhagata Choudhury ◽  
...  

AbstractBackgroundis a popular fruit plant in the Indian subcontinent, various parts of which are traditionally used against various illnesses including diabetes mellitus (DM). However, the underlying mechanisms of the antidiabetic effects of the plant are not clear, especially in type 2 DM. The present study was undertaken to investigate the effect of aqueous extracts ofMethodsAn interventional study was designed using 20 type 2 diabetic rats. Type 2 DM was induced in Long Evans rats by a single intra-peritoneal injection of streptozotocin (90 mg/kg body weight) to 48 h old pups. Three months after induction of diabetes, the rats were divided into three independent groups: water-treated control group (n=6), AMLE-treated group (n=7) and AMFE-treated group (n=7). The rats were fed with extracts or water for 21 consecutive days and blood samples were collected at days 0 and 21 after an overnight fast. Data were expressed as mean±SD and analyzed by paired t-test or ANOVA as appropriate.ResultsThere were significantly lower blood glucose values in AMLE and AMFE groups at Endpoint compared to Baseline (mmol/l, mean±SD, Baseline vs. Endpoint, 7.04±1.0 vs. 6.06±0.92; p=0.032 and 7.04±0.97 vs. 5.87±0.93; p=0.047). There were also significantly lower serum insulin levels in AMLE and AMFE groups at Endpoint compared to Baseline (µIU/mL, mean±SD, Baseline vs. Endpoint, 14.02±5.48 vs. 7.57±2.90; p=0.026 and 11.54±4.83 vs. 6.58±4.36; p=0.008). Insulin resistance (HOMA-IR) was significantly improved both in AMLE and AMFE groups at Endpoint compared to Baseline (mean±SD, Baseline vs. Endpoint, 4.22±1.68 vs. 2.05±0.90; p=0.021 and 3.69±1.79 vs. 1.69±1.61; p=0.013). However, β-cell function or lipid profile did not show any significant alteration at Endpoint compared to Baseline in AMLE and AMFE groups.ConclusionsAqueous extracts of


2014 ◽  
Vol 989-994 ◽  
pp. 1015-1019
Author(s):  
Xu Sheng Li ◽  
Ren Yan Wu ◽  
Ye Hu

To investigate the effects of Ginkgo biloba extract (GbE) on the activities of energy metabolism enzymes and contraction capacity of diaphragm from type 2 diabetic rats. Forty SD mile rats were randomly divided into normal control group (n=10) and model group (n=30). Type 2 diabetes models were induced by feeding with high-sucrose-high-fat diet and intraperitoneal injecting 25mg/kg streptozotocin. 20 successful models were rearranged to two groups: diabetic group and GbE treatment group, 10 rats in each. Then the saline and 8mg·kg-1·d-1 of GbE were respectively intraperitoneal injected, once a day continuously for 8 weeks. Then diaphragm contractility was assessed using Peak twitch tension (Pt), Maximum tetanic tension (P0) and fatigue index (FI) in vitro diaphragm strip preparations. Cytochrome oxidase (CCO), lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in diaphragm were detected and the varieties of diaphragm ultrastructure were observed. Compared with control group, Pt, P0 and FI in diabetic group decreased significantly (P < 0.01); the activity of CCO, LDH and SDH in the tissues was obviously reduced than those in control group (P < 0.01). The ultrastructure in diabetic group under electron microscope indicated that diaphragm mitochondrions swelled and degenerated. The above changes were inhibited by GbE. GbE can enhance contraction capacity of diaphragm from type 2 diabetic rats by increasing the aerobic oxidation capacity, glycolytic capacity and the function of respiratory chain.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Maxwell Omabe ◽  
Chibueze Nwudele ◽  
Kenneth Nwobini Omabe ◽  
Albert Egwu Okorocha

Moringa oleifera (MO) is used for a number of therapeutic purposes. This raises the question of safety and possible toxicity. The objective of the study was to ascertain the safety and possible metabolic toxicity in comparison with metformin, a known drug associated with acidosis. Animals confirmed with diabetes were grouped into 2 groups. The control group only received oral dose of PBS while the test group was treated with ethanolic extract of MO orally twice daily for 5-6 days. Data showed that the extract significantly lowered glucose level to normal values and did not cause any significant cytotoxicity compared to the control group (P=0.0698); there was no gain in weight between the MO treated and the control groups (P>0.8115). However, data showed that treatment with an ethanolic extract of MO caused a decrease in bicarbonate (P<0.0001), and more than twofold increase in anion gap (P<0.0001); metformin treatment also decreased bicarbonate (P<0.0001) and resulted in a threefold increase in anion gap (P<0.0001). Conclusively, these data show that while MO appears to have antidiabetic and noncytotoxic properties, it is associated with statistically significant anion gap acidosis in alloxan induced type 2 diabetic rats.


2020 ◽  
Vol 24 (3) ◽  
pp. 174-184
Author(s):  
Dara Dastan ◽  
◽  
Iraj Salehi ◽  
Alireza Komaki ◽  
Alireza Gharib ◽  
...  

Introduction: Diabetes mellitus (DM) is one of the most frequent metabolic diseases that affect various body systems. Cognitive impairment caused by diabetes is gaining more acceptance and attention. In this study, we have investigated the effects of a traditionally herbal formulation (THF) on oxidative stress (OS) and cognitive deficits in type 2 diabetic rats. Methods: Thirty-six male Wistar rats were divided into six groups: control group, diabetic group, diabetic+100, 200 or 300mg/kg THF, diabetic+glibenclamide (G) 5mg/kg. Streptozotocin-nicotinamide was used to induce type-II diabetes mellitus. Spatial and passive avoidance learning and memory function were evaluated by Morris Water Maze (MWM), novel object recognition test (NORT) and open field test (OFT). The OS biomarkers were also analyzed. The THF was standardized using RP-HPLC according to phenolic and flavonoids compounds. Results: Indicated that in the diabetic treated (300mg/kg THF and G) vs. diabetic groups, body weight and insulin were significantly increased and the levels of fasting blood glucose significantly reduced. OS was improved in the treated (300mg/kg THF) groups. Furthermore, we noticed that diabetic treated groups (300mg/kg THF) vs. diabetes caused in significant decreases of the travelled distance and escape latency to find the hidden platform, also increased in the time spent and travelled distance in the target quadrant in MWM test, exploration time in NORT and total distance moved in OFT. Conclusion: These findings suggest that THF ameliorated learning and memory deficits in type 2 diabetic rats via reducing OS. THF can be used with a caution against human DM.


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