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Department of medicine, Educare institute of dental science Malappuram, Kerala and SafeCare clinics, Tirur, Keralasulfonylureas (SUs) are one of the oldest, time tested and most commonly used oral antidiabetic agent in Type 2 diabetes. Modern SUs like glimepiride and gliclazide XR were preferred over conventional SUs due to its better efficacy and minimal side effects. The use of Modern SUs in the treatment armamentarium of T2DM has evolved, over past few decades. Modern SUs possesses beneficial pancreatic glucose lowering effect and more interestingly extra-pancreatic pleiotropic benefits. This review article discusses on the utility and benefits of SUs beyond glycemic control and explaining on their pleiotropic effects.
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Objective: To develop and validate novel more sensitive analytical methods for the concurrent quantification of metformin-canagliflozin and metformin-gliclazide in their bulk forms and in their pharmaceutical preparations. Methods: Two methods were developed based on several chemometric assisted spectrophotometric methods and a Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC). The first method applies different spectrophotometric chemometric assisted methods, including ratio difference, derivative ratio and extended ratio subtraction method, while the second method describes a RP-HPLC separation of metformin hydrochloride-canagliflozin and metformin hydrochloride-gliclazide binary mixtures using a C18 column with a mobile phase consisting of acetonitrile: potassium dihydrogen phosphate (adjusted to pH 3) with sodium lauryl sulphate as additive in the ratio of 30:70 (%v/v) in isocratic elution mode at 1 ml/min. Results: The proposed methods were able to quantify each of the studied drugs in their binary mixtures with high percentage recoveries in both methods. The spectrophotometric methods were able to quantify each of metformin, canagliflozin and gliclazide in the ranges of 2.0-20.0 μg/ml, 1.5-40.0 μg/ml and 2.0-30.0 μg/ml, respectively. The RP-HPLC method produced well-resolved peaks at a retention time of 3.92, 6.92 and 9.10 min in the concentration ranges of 50.0-300.0 μg/ml, 5.0-50.0 μg/ml and 10.0-100.0 μg/ml for metformin, canagliflozin and gliclazide, respectively. The proposed methods were optimized and validated in accordance to the International Conference of Harmonisation (ICH) guidelines in terms of linearity, LOD, LOQ, precision and accuracy. Conclusion: The developed methods were found to be sensitive and reproducible methods for the simultaneous determination of anti-diabetic binary mixtures; metformin hydrochloride-canagliflozin and metformin hydrochloride-gliclazide. And thus were successfully employed for the quality control analysis of the pharmaceutical formulations of the studied binary mixtures.
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Objective: To explore the pharmacokinetics of self-made gliclazide modified release tablets in Beagle dogs and to evaluate the in vivo and in vitro correlation. Methods: Six Beagle dogs were orally given self-made gliclazide modified release tablets or reference preparation (DaMeiKang) at a dose of 30 mg with self-control cross-over method. Blood samples were collected at different time points after administration. The gliclazide concentration in plasma was determined by high-performance liquid chromatography, and the pharmacokinetic parameters were calculated. The pharmacokinetic characteristics and relative bioavailability of self-made gliclazide modified release tablets were investigated, the bioequivalence was evaluated, and the in vivo and in vitro correlation was calculated. Results: Area under curve (AUC0-∞) of DaMeiKang was (101.74 ± 20.29) μg/(mL · h), and AUC0-∞ of self-made gliclazide modified release tablets was (95.40 ± 28.68) μg/(mL · h). There were no significant differences in the pharmacokinetic parameters between the test and reference formulations (P>0.05). The relative bioavailability of self-made gliclazide modified release tablets was 93.77%, which was bioequivalent with the reference preparation. The in vitro and in vivo correlation analysis showed that the correlation coefficients of DaMeiKang and self-made gliclazide modified release tablets were 0.912 and 0.894, respectively, which were higher than the critical value (r005.7=0.754). The in vitro release rates of the two preparations were correlated with the in vivo absorption rates. Conclusion: The self-made gliclazide modified release tablets have sustained-release characteristics and bioequivalence with reference preparation. The in vivo absorption behavior of gliclazide modified release tablets can be predicted by the in vitro release assay established in this study.
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A mucosite oral (MO) é uma inflamação aguda da mucosa oral, sequela mais importante dos tratamentos de radioterapia ou/e quimioterapia. As lesões na cavidade oral são graves, dolorosas e podem levar a sepse e morte. Não existe um protocolo único de prevenção e cura para MO. Na perspectiva de encontrar terapias farmacológicas para prevenir MO, propomos a investigação do efeito pleiotrópico do medicamento comercial gliclazida, um anti-diabético de ação secundária anti-inflamatória e antioxidante nunca estudada na MO. Este estudo teve como objetivo avaliar o efeito da gliclazida em um modelo MO experimental induzido por 5-fluorouracil. Hamsters machos foram pré-tratados com gliclazida oral (1, 5 ou 10mg/kg) por 10 dias. As amostras das mucosas dos animais foram submetidas à análise macroscópica, histopatológica e imuno-histoquímica (COX2, iNOS, MMP-2, NFκB P65, GPx) e imunofluorescência (P-selectina). Os níveis de IL-1ß e TNF-α, a atividade de mieloperoxidase (MPO) e os níveis de malondialdeído (MDA) foram investigados por análise espectroscópica ultravioleta-visível. A expressão protéica de NFκB NLS P50 foram analisados por western blotting. O grupo tratado com gliclazida na dose de 10 mg / kg apresentou melhores resultados como ; presença de eritema, ausência de erosão e de ulceração da mucosa com escore de 1 (1-2) (p <0,01) nos achados clínicos. Os dados histopatológicos do grupo tratado com gliclazida 10 mg / kg mostraram reepitelização, discreto infiltrado inflamatório mononuclear, úlceras com escore de 1 (1-1) (p <0,01). O tratamento com gliclazida 10 mg/kg reduziram os níveis de atividade de MPO (p <0,001), MDA (p <0,001) e NFκB NLS P50 (p <0,05), resultando em baixa imunocoloração para Cox-2, iNOS (p <0,05) , NFκB P65 (p <0,05) e imunorreacção negativa para MMP-2 (p <0,001).Para Gpx, a coloração foi menos intensa no grupo GLI 10-FUT em comparação com 5FUT/solução salina (p <0,05). A Imunofluorescência revelou diminuição dos níveis de P-selectina (p <0,001) após o tratamento com gliclazida 10 mg/kg (p <0,05). A gliclazida na dose de 10mg/kg atenuou a severidade da MO e reduziu o estresse oxidativo e a inflamação na MO induzida pelo 5-FU em hamsters (AU).
Oral mucositis (OM) is acute inflammation of the oral mucosa, the most important sequelae from radiotherapy and/or chemotherapy treatments. The lesions in the oral cavity are severe and painful, and can lead to sepsis and death. There is no single protocol for preventing or curing OM. From the perspective of finding pharmacological therapies to prevent OM, we propose an investigation of the pleiotropic effect of commercial drugs, among them gliclazide, an anti-diabetic with anti-inflammatory and anti-oxidant side action which has never studied regarding OM. This study aimed to evaluate the effect of gliclazide on an experimental OM model induced by 5-fluorouracil. Male hamsters were pretreated with oral gliclazide (1, 5 or 10 mg/kg) for 10 days. The mucosal samples of the animals were submitted to histopathological and immunohistochemical analysis (COX2, iNOS, MMP-2, NFκB P65, GPx) and immunofluorescence (P-selectin). Levels of IL-1ß and TNF-α, myeloperoxidase activity (MPO) and malondialdehyde levels (MDA) were investigated by ultraviolet-visible spectroscopic analysis. Protein expression of NFkB NLS P50 was analyzed by western blotting. The group treated with gliclazide at a dose of 10 mg/kg presented erythema, absence of erosion and mucosal ulceration with a score of 1 (1-2) (p <0.01) in the clinical findings. The histopathological data of the gliclazide 10 mg/kg group showed reepithelialization, a discrete mononuclear inflammatory infiltrate, and ulcers with a score of 1 (1-1) (p <0.01). Treatment with 10 mg/kg gliclazide reduced the activity levels of MPO (p <0.001), MDA (p <0.001) and NFκB NLS P50 (p <0.05), resulting in low immunostaining for Cox-2, iNOS (p <0.05), NFκB P65 (p <0.05) and negative immunoreaction for MMP-2. For Gpx, staining was restored in the GLI 10-FUT group compared to 5FUT/saline (p <0.05). Immunofluorescence showed a decrease in P-selectin levels (p <0.001) after treatment with 10 mg/kg gliclazide (p <0.05). Furthermore, 10 mg/kg gliclazide attenuated OM severity and reduced oxidative stress, and 5-FU induced OM in hamsters (AU).
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Animals , Rats , Stomatitis/pathology , Immunohistochemistry , Anti-Inflammatory Agents/pharmacology , Blotting, Western , Analysis of Variance , Fluorescent Antibody Technique , Statistics, NonparametricABSTRACT
Objective To investigate the clinical effect of mefformin tablets in the treatment of type 2 diabetes mellitus(T2DM) with atherosclerosis.Methods A total of 84 T2DM patients with atherosclerosis were divided into control group and treatment group according to the random number table method,42 cases in each group.All patients were given diet control,health education and exercise,etc..The control group was treated with gliclazide sustained-release tablets.The treatment group was treated with mefformin and treated for 6 months.The levels of fasting blood glucose(FBG) and 2 h postprandial blood glucose(2hPBG) were measured before and 6 months after treatment.The levels of intima-media thickness (cIMT),leptin (LP),adiponectin (TC),chitinase-3-like protein-1 (YKL-40),triglyceride (TG),low density lipoprotein cholesterol (HDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured.The adverse reactions were observed in the two groups.Results After treatment for 6 months,the levels of FBG and 2hPBG in the treatment group were (6.71 ±0.41) mmol/L and (8.82 ±0.61) mmol/L,respectively,which were significantly lower than those in the control group [(6.96 ± 0.48) mmol/L,(9.58 ± 0.57) mmol/L,t =2.56,5.89,P =0.01,0.00].The levels of cIMT,TC,TG and LDL-C in the treatment group were significantly lower than those in the control group at 6 months after treatment (t =5.36,6.46,9.10,2.31,P =0.00,0.00,0.00,0.02).After 6 months of treatment,the HDL-C level of the treatment group was significantly higher than that of the control group (t =2.84,P =0.00).After treatment for 6 months,HDL-C level in the two groups was significantly higher than before treatment,the other indicators in the two groups were significantly lower than before treatment (all P ＜ 0.05).There were no adverse reactions in the two groups during treatment.Conclusion Metformin in the treatment of T2DM patients with atherosclerosis has significant effect,it can improve blood glucose levels and the clinical and biochemical indicators,and it is safe.
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Objective To explore the clinical efficacy of combination therapy with promethrin and gliclazide sustained-release tablets in the treatment of obese patients with type 2 diabetes mellitus with poor blood glucose control. Methods Selected from December 2015 to March 2017 in our hospital treated 96 cases of insulin treatment of poor blood glucose control in obese patients with type 2 diabetes, were randomly divided into study group and control group, 48 cases in each group.The study group were treated with Novolin 70/30(Novolin 30R)combined with Gliclazide Sustained-release Tablets,while the patients in control group were treated with Novolin 30R combined with repaglinide. Results The decrease of FBG, 2h PG, HbAlc, HOMA-IR and the increase of HOMA-IS in the study group were better than those in the control group (P<0.05).There was no significant difference in BMI between the two groups after treatment and BMI in the control group was significantly higher than that before treatment (P<0.05),CRP was not statistically significant before treatment.Conclusion The application of Novolin 30R and Gliclazide Sustained-release Tablets after treatment can make the use of insulin alone poor glycemic control in obese patients with type 2 diabetes have more desirable clinical efficacy,is conducive to ensuring the safety and effectiveness of drugs.
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Objective To investigate the effect of psychological intervention combined with gliclazide and sitagliptin on the treatment of poorly obese obese patients with type 2 diabetes mellitus. Methods 96 obese patients with type 2 diabetes mellitus who had poor control of blood glucose after insulin treatment were randomly divided into control group and experimental group,48 cases in each groups. Gliclazide and sitagliptin (FBG), glycosylated hemoglobin (HbA1c), 2h postprandial blood glucose (2hPG), fasting insulin (FIns) were measured before and after 15 weeks of treatment in the control group. situation. Results FBG, HbA1c, 2hPG and FIns were significantly lower in the experimental group than in the control group (P<0.05). Conclusion The combination of gliclazide and sitagliptin on the treatment of poorly obese type 2 diabetes mellitus with insulin treatment can significantly reduce the blood glucose level of patients and promote it.
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Objective To explore the effect of gliclazide and Sig Leo Dean on insulin treatment for poor glycemic control in obese patients with type 2 diabetes mellitus. Methods 80 cases of insulin treatment for poor glycemic control in obese patients with type 2 diabetes mellitus treated in our hospital from March 2015 to January 2017 were randomly divided into two groups,with 40 cases in each group.The control group was treated with gliclazide The observation group was treated with Sig Leo Dean.The therapeutic effects of the two groups were observed and compared. Results 2 hours postprandial blood glucose levels improved in the observation group was better than that of the control group, the body weight, blood pressure, fasting blood glucose of two groups were improved, and there were no significant difference between the two groups; The incidence rate of adverse reactions was 2.5% in the observation group, 10% in the control group, the difference was not statistically significant (P<0.05). Conclusion Analysis of gliclazide and Sig Leo Dean on insulin treatment for poor glycemic control in obese patients with type 2 diabetes mellitus curative effect, Sig Leo Dean for the glycaemic improvement effect is higher, reduce the incidence of adverse reactions, so more medication safety, it is worthy of clinical promotion Application.
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Objective To observe the clinical effect of pioglitazone combined with gliclazide sustained-release tablets in the treatment of patients with early type 2 diabetes mellitus.Methods 80 patients with early type 2 diabetes mellitus in our hospital from June 2013 to July 2016 were selected as the study object,and the patients were randomly divided into two groups, 40 cases in each group.The control group were treated with gliclazide sustained-release tablets, the observation group were treated with pioglitazone combined with gliclazide sustained-release tablets.Then the blood glucose level, glycosylated hemoglobin level, lipid metabolism indexes and islet function indexes of two groups before and after the treatment were detected and compared.Results The blood glucose level, glycosylated hemoglobin level, lipid metabolism indexes and islet function indexes of two groups before the treatment were compared, the difference was statistically significant (P<0.05), while the blood glucose level, glycosylated hemoglobin level, lipid metabolism indexes and islet function indexes of two groups after the treatment were continuously improved , and the blood glucose level and glycosylated hemoglobin level of observation group were lower than those of control group, the ipid metabolism indexes and islet function indexes were all better than those of control group, the difference was statistically significant (P <0.05).Conclusion The clinical effect of pioglitazone combined with gliclazide sustained-release tablets in the treatment of patients with early type 2 diabetes mellitus is better, and it also has active adjustion role for the blood glucose, blood lipid and islet function state.
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Objective: To develop an HPLC method with solid nuclear particle chromatographic column to determine 13 anti-diabetic drugs illegally added in health food. Methods: The analysis was performed by an HPLC system of Waters e2695, with Cortecs-C18 (100 mm × 4.6 mm, 2.7 μm) column. PDA was performed to identify and quantify tolbutamide, glibenclamide, gliclazide, glipizide, gliquidone, glimepiride, rosiglitazone, repaglinide, pioglitazone hydrochloride, metformin, phenformin, buformin hydrochloride, and glibomuride, which were extracted with methanol by ultrasonic. Results: Thirteen linear calibration curves were obtained with r2 ≥ 0.998 7. The precision of the method was shown by RSD (n = 6) ranged from 0.6% to 1.5%. The recoveries were determined at three concentrations and ranged from 95.9% to 104.7%. The ranges of LLOQ were from 1.1 μg/mL to 3.3 μg/mL and the RSDs (n = 9) of inter-day precision were from 0.5% and 1.6%. Seventeen batches in 86 antidiabetic health foods were added the chemicals with positive rate of 20%. The glibenclamide, buformin hydrochloride, rosiglitazone, glimepiride, metformin, and pioglitazone hydrochloride were determined. Conclusion: The method is specific, simple, and fast to detect 13 anti-diabetic drugs illegally added in health food.
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Gliclazide used for the treatment of type 2 diabetes mellitus (T2DM) stimulates insulin secretion and influences peripheral blood monocytes.The roles of gliclazide in peripheral monocytes of newly diagnosed T2DM patients were investigated in this study.A total of 105 newly diagnosed T2DM patients with no history of antihyperglycemic medication were treated with gliclazide-modified release for 16 weeks.The total and differential leukocyte profiles of peripheral blood were measured at baseline and week 16.The peripheral blood monocyte count at week 16 was significantly lower than that at baseline (P=0.019).Peripheral monocytes level at baseline was positively correlated with waist circumference.After gliclazide treatment,the peripheral monocytes were decreased [(320.09±15.13)×106/L vs.(294.19±14.22)×106/L] in non-abdominal obesity group,but increased in abdominal obesity group [(344.36±17.24)×106/L vs.(351.87±16.93)×106/L].Compared with non-abdominal obese patients,abdominal obese patients showed higher Amonocytes (P=0.046) and Aacute insulin secretion (P=0.049),but lower AHbAlc (P=0.047).There was significantly positive correlation between Amonocytes and Aacute insulin secretion (P=0.015),which disappeared after adjusting for age,waist circumference and dosage at baseline.In conclusion,waist circumference is correlated with peripheral monocyte change after gliclazide treatment in Chinese newly diagnosed T2DM patients.Peripheral monocytes are decreased in non-abdominal obesity group and increased in abdominal obesity group after gliclazide treatment.
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Enterococci, a low-grade pathogen, emerged as a potent nosocomial agent and have recently drawn the global attention because of resistance issues. To deal with this serious threat and reversal of drug sensitivity pattern, we made an attempt to sensitize the cells of Enterococcus faecalis with an oral hypoglycemic molecule gliclazide belonging to the class sulfonylurea. Interestingly, it was observed that results were quite encouraging as it was able to enhance gentamicin sensitivity by reducing the minimum inhibitory concentration (MIC). The decrease in MIC of gentamicin to E. faecalis is an indicator of reversibility of drug resistance. The findings have confirmed the concept that prior course or combination therapy of oral hypoglycemic drug with antibiotic gentamicin can be effective against Enterococci strains. However, auxiliary tests still need to be carried out further to understand the exact mechanism of the enhancement procured by gliclazide. The results have sowed the seeds of the concept of using gliclazide as a drug-resistant reversal molecule.
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Objective:To observe the effect and influence of homocysteine and cystatin C in type 2 diabetes patients treated by Shuxuening injection combined with gliclazide. Methods: Type 2 diabetic patients were randomly divided into observation group and control group,and there were 30 cases in each group. The control group was given gliclazide hypoglycemic treatment, on the basis of the observation group to combined with Shuxuening injection. The course of treatment was 2 weeks. Efficacy , adverse drug reactions ,Ho-mocysteine ( Hcy) , Cystatin C ( CysC) and blood glucose ( FBG, PB) level change of two groups patients before and after treatment were compared. Results:The total effective rate of the observation group was 96. 67%, which was significantly higher than that of the control group (P0. 05). Conclusion:Shuxuening Injection on patients with type 2 diabetes mellitus has good curative effect, it can effectively reduce homocysteine and cystatin C levels, better control of blood glucose.
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[Summary] To investigate the effect of gliclazide on the proliferation and differentiation in MC3T3-E1 cells exposed to normal glucose concentration by applying CCK-8 and RT-PCR. Gliclazide improved the proliferation and stimulated COL-I, OPN and Runx2 mRNA expression in MC3T3-E1 cells, the best concentration of gliclazide was 20μmol/ L, the expression of COL-1 and OPN mRNA had a significant positive correlation with Runx2 binding activity.
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@#In this study, coamorphous simvastatin-gliclazide was prepared and characterized. Its single-phase amorphous nature was demonstrated. The hydrogen bond between the O-H group of simvastatin and sulfonylurea C=O group of gliclazide was revealed to be the trigger for the amorphization of gliclazide, which is difficult to form an amorphous state in other methods. Coamorphous simvastatin-gliclazide can significantly enhance the solubility and dissolution of gliclazide, without obvious effect on simvastatin. Compared with amorphous simvastatin, coamorphous simvastatin-gliclazide showed improved physical stability in the cunrent study.
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This study aimed to formulate, characterize and evaluate the Gliclazide (GLZ) microcapsules prepared with sodium alginate, guar gum and pectin in different ratios by ionotropic-gelation method. The microcapsules were evaluated against different parameters such as particle size and shape, Carr's index, Hausner's ratio, rheological studies and drug release kinetics. Fourier Transform Infra Red (FTIR) and Differential Scanning Calorimetric (DSC) studies demonstrated the absence of any drug - polymers interaction. Promising characteristics were observed in rheological behavior and release kinetics. The size of microcapsules and percentage yield was in the range of 676 to 727 µm and 69 to 77%, respectively. Scanning electron micrographs revealed that microcapsules were discrete, spherical and free flowing. Entrapment efficiency and uniform drug release kinetics were some of the probable characteristics depicting the novel formulation design of Gliclazide microcapsules.
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Physalis peruviana Linn in Indonesia was better known as ciplukan, based on information from urban people in Indonesia is as antidiabetic. In the previeous studies, the levels of blood glucose in animals experimental of Physalis peruviana quantified with glucometer and compared with oral antidiabetic drugs gliclazide, showed that Gliclazide was decrease more levels of glucose significantly than ethanol extract of Physalis peruviana. We have done molecular docking using Molegro Virtual Docker (MVD) on ethanol extract of Physalis peruviana and gliclazide to compare between in silico and in vivo studies. Based on studies before the main content of the ethanol extract of Physalis peruviana were withanolide, 4-OH-withanolide, and perulactone. In this study the results showed that gliclazide had been better bond in insulin tyrosine kinase receptor than main content of Physalis peruviana which can be seen from Moldock score 105.217 and Rerank score -68,2931 means that the energy was lower and more stable binding. Moldock Score of main content Physalis peruviana (withanolide, 4-OH-withanolide, and perulactone) were -93.5472; 70.5843; 88.7881, respectively. Rerank score of main content Physalis peruviana (withanolide, 4-OH-withanolide, and perulactone) were -61.5149; -67.5345; -65.7979, respectively. The hydrogen bonds of withanolide, 4-OH-withanolide, perulactone and gliclazide with amino acid of insulin tyrosine kinase receptor were Phe 1186 and Thr 1186. Finally, in the 3D MVD visualization between main content of ethanol extract of Physalis peruviana and gliclazide can be concluded that interaction of gliclazide was more harmonious than main content of ethanol extract Physalis peruviana.
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Objective:To evaluate the clinical efficacy and safety of repaglinide and gliclazide in the treatment of elderly type 2 di-abetes mellitus (T2DM). Methods:A total of 225 T2DM patients with the age over 60 were enrolled and randomly divided into repa-glinide group (n=112) and gliclazide group (n=113). The repaglinide group was given repaglinide 0. 5~2 mg, po, tid, while the gliclazide group was given gliclazide modified release tablets 30~120 mg, po, qd,both with the treatment course of 12 weeks. The level of FPG, 2h PG, HbAlC, TC and TG and the side effects were observed and the clinical efficacy was compared between the two groups. Results:The level of FPG, 2h PG, HbAlc and TC in the two groups showed significant decrease after the treatment (P0. 05). Conclusion:Both repaglinide and gliclazide show safe and reliable efficacy in the treatment of elderly T2DM.
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AIM:To investigate the effect of insulin and gliclazide therapies on the liver fat accumulation in type 2 diabetic rats .METHODS:A high-fat diet plus low-dose streptozotocin was implemented to establish a type 2 dia-betic rat model, and the rats were randomly divided into diabetes mellitus (DM) group, diabetic rats treated with insulin ( INS) group, diabetic rats treated with gliclazide per os ( PO) group, and normal control ( NC) group.The diabetic rats in INS group and PO group were given insulin and gliclazide for 3 weeks, respectively.The changes of the liver fatty were evaluated with oil red O staining .Fasting plasma adiponectin concentration was measured by ELISA .The expression of adi-ponectin receptor 1 ( AdipoR1 ) was detected by real-time PCR.The protein levels of AMP-activated protein kinase (AMPK), phosphorylated AMPK on threonine 172 ( Thr172p-AMPK), sterol regulatory element-binding protein 1c (SREBP-1c), phosphorylated SREBP-1c on serine 372 (Ser372p-SREBP-1c), acetyl-CoA carboxylase (ACC), phospho-rylated ACC on serine79 (Ser79p-ACC) and immunoglobulin-binding protein (BiP) in the liver homogenate were deter-mined by Western blotting .RESULTS:Compared with the normal rats , in DM group, the presence of cytoplasmic lipid deposits was confirmed by oil red O staining .In INS group, these changes were significantly lower than those in DM group . Similar results were obtained in PO group .Insulin therapy significantly increased the plasma concentration of diponectin and liver tissue levels of AdipoR1 compared with DM group.At the same time, these 2 indicators returned to normal levels after gliclazide therapy .Thr172p-AMPK/AMPK, Ser372p-SREBP-1c/SREBP-1c and Ser79p-ACC/ACC expression ratios were significantly reduced in DM group compared with control values .The expression of BiP was increased on the contrary . After insulin therapy, Thr172p-AMPK/AMPK and Ser372p-SREBP-1c/SREBP-1c were significantly increased, and Ser79p-ACC/ACC and BiP returned to the normal levels .After gliclazide treatment, Thr172p-AMPK/AMPK and Ser372p-SREBP-1c/SREBP-1c returned to the normal levels , the expression ratio of Ser79p-ACC/ACC had no significant improve-ment compared with DM group , and the expression of BiP significantly declined .CONCLUSION: Both the insulin and gliclazide therapies reduce the lipid deposition in the liver of rats with type 2 diabetes by activating AMPK , but the extent and mechanism are not the same.In insulin therapy, AMPK restrains the expression of SREBP-1c directly, increases the phosphorylation of SREBP-1c, and affects SREBP-1c by inhibiting the endoplasmic reticulum stress .Gliclazide treatment, which has no effect on the lipid oxidation , reduces lipid deposition in the liver only through the phosphorylation of SREBP-1c and the suppression of the endoplasmic reticulum stress .
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Physalis peruviana Linn in Indonesia was better known as ciplukan, based on information from urban people in Indonesia is as antidiabetic. In the previeous studies, the levels of blood glucose in animals experimental of Physalis peruviana quantified with glucometer and compared with oral antidiabetic drugs gliclazide, showed that Gliclazide was decrease more levels of glucose significantly than ethanol extract of Physalis peruviana. We have done molecular docking using Molegro Virtual Docker (MVD) on ethanol extract of Physalis peruviana and gliclazide to compare between in silico and in vivo studies. Based on studies before the main content of the ethanol extract of Physalis peruviana were withanolide, 4-OH-withanolide, and perulactone. In this study the results showed that gliclazide had been better bond in insulin tyrosine kinase receptor than main content of Physalis peruviana which can be seen from Moldock score 105.217 and Rerank score -68,2931 means that the energy was lower and more stable binding. Moldock Score of main content Physalis peruviana (withanolide, 4-OH-withanolide, and perulactone) were -93.5472; 70.5843; 88.7881, respectively. Rerank score of main content Physalis peruviana (withanolide, 4-OH-withanolide, and perulactone) were -61.5149; -67.5345; -65.7979, respectively. The hydrogen bonds of withanolide, 4-OH-withanolide, perulactone and gliclazide with amino acid of insulin tyrosine kinase receptor were Phe 1186 and Thr 1186. Finally, in the 3D MVD visualization between main content of ethanol extract of Physalis peruviana and gliclazide can be concluded that interaction of gliclazide was more harmonious than main content of ethanol extract Physalis peruviana.