scholarly journals The Biological Impacts of Sitagliptin on the Pancreas of a Rat Model of Type 2 Diabetes Mellitus: Drug Interactions with Metformin

Biology ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 6 ◽  
Author(s):  
Lamiaa M. Shawky ◽  
Ahmed A. Morsi ◽  
Eman El Bana ◽  
Safaa Masoud Hanafy
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Rat Model ◽  
Cell Damage ◽  
Diabetic Rats ◽  
Male Rats ◽  
Control Group ◽  
Dipeptidyl Peptidase 4

Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is a beneficial class of antidiabetic drugs. However, a major debate about the risk of developing pancreatitis is still existing. The aim of the work was to study the histological and immunohistochemical effects of sitagliptin on both endocrine and exocrine pancreases in a rat model of type 2 diabetes mellitus and to correlate these effects with the biochemical findings. Moreover, a possible synergistic effect of sitagliptin, in combination with metformin, was also evaluated. Fifty adult male rats were used and assigned into five equal groups. Group 1 served as control. Group 2 comprised of untreated diabetic rats. Group 3 diabetic rats received sitagliptin. Group 4 diabetic rats received metformin. Group 5 diabetic rats received both combined. Treatments were given for 4 weeks after the induction of diabetes. Blood samples were collected for biochemical assay before the sacrification of rats. Pancreases were removed, weighed, and were processed for histological and immunohistochemical examination. In the untreated diabetic group, the islets appeared shrunken with disturbed architecture and abnormal immunohistochemical reactions for insulin, caspase-3, and inducible nitric oxide synthase (iNOS). The biochemical findings were also disturbed. Morphometrically, there was a significant decrease in the islet size and islet number. Treatment with sitagliptin, metformin, and their combination showed an improvement, with the best response in the combined approach. No evidence of pancreatic injury was identified in the sitagliptin-treated groups. In conclusion, sitagliptin had a cytoprotective effect on beta-cell damage. Furthermore, the data didn’t indicate any detrimental effects of sitagliptin on the exocrine pancreas.

scholarly journals Role of TLR4/MyD88/NF-κB signaling in heart and liver-related complications in a rat model of type 2 diabetes mellitus

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199759
Author(s):  
Jiajia Tian ◽  
Yanyan Zhao ◽  
Lingling Wang ◽  
Lin Li
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Rat Model ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Primary Response ◽  
Monocyte Chemoattractant Protein 1

Aims To analyze expression of members of the Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/nuclear factor (NF)-κB signaling pathway in the heart and liver in a rat model of type 2 diabetes mellitus (T2DM). Our overall goal was to understand the underlying pathophysiological mechanisms. Methods We measured fasting blood glucose (FBG) and insulin (FINS) in a rat model of T2DM. Expression of members of the TLR4/MyD88/NF-κB signaling pathway as well as downstream cytokines was investigated. Levels of mRNA and protein were assessed using quantitative real-time polymerase chain reaction and western blotting, respectively. Protein content of tissue homogenates was assessed using enzyme-linked immunosorbent assays. Results Diabetic rats had lower body weights, higher FBG, higher FINS, and higher intraperitoneal glucose tolerance than normal rats. In addition, biochemical indicators related to heart and liver function were elevated in diabetic rats compared with normal rats. TLR4 and MyD88 were involved in the occurrence of T2DM as well as T2DM-related heart and liver complications. TLR4 caused T2DM-related heart and liver complications through activation of NF-κB. Conclusions TLR4/MyD88/NF-κB signaling induces production of tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1, leading to the heart- and liver-related complications of T2DM.

scholarly journals IMPROVEMENT IN OXIDATIVE STRESS AFTER DUODENOJEJUNOSTOMY IN AN EXPERIMENTAL MODEL OF TYPE 2 DIABETES MELLITUS

2016 ◽  
Vol 29 (suppl 1) ◽  
pp. 3-7 ◽  
Author(s):  
Cacio Ricardo WIETZYCOSKI ◽  
João Caetano Dallegrave MARCHESINI ◽  
Sultan AL-THEMYAT ◽  
Fabiola Shons MEYER ◽  
Manoel Roberto Maciel TRINDADE
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Control Group ◽  
Oral Glucose ◽  
Surgical Group

ABSTRACT Background: Type 2 Diabetes Mellitus is a multifactorial syndrome with severe complications. Oxidative stress is accepted as a causal factor of chronic complications Aim: To demonstrate alterations in oxidative stress after metabolic surgery. Methods: Twenty-four 2-day-old Wistar rats were used. In 16, Type 2 Diabetes Mellitus was induced by 100 mg/kg streptozotocin injection. The development of diabetes was confirmed after 10 weeks using an oral glucose tolerance test. Eight diabetic rats composed the diabetic surgical group; the remaining eight composed the diabetic group. Eight animals in which diabetes was not induced formed the clinical control group. The Marchesini technique was used in the diabetic surgical group. After 90 days, the rats were sacrificed, and the oxidative stress markers were measured. Results: Thiobarbituric acid reactive substances, superoxide dismutase and catalase were significantly reduced in the diabetic surgical group compared to the diabetic group. Conclusion: The duodenojejunostomy was effective in controlling the exacerbated oxidative stress present in diabetic rats.

scholarly journals Cardiovascular risk of sitagliptin in treating patients with type 2 diabetes mellitus

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
De-kang Zeng ◽  
Qian Xiao ◽  
Fa-qi Li ◽  
Yu-zhi Tang ◽  
Chao-li Jia ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Clinical Trials ◽  
Type 2 Diabetes Mellitus ◽  
Cardiovascular Events ◽  
Secondary Outcome ◽  
Control Group ◽  
Dipeptidyl Peptidase 4 ◽  
Significant Difference

Abstract Patients with type 2 diabetes mellitus (T2DM) have a very high risk of cardiovascular related events, and reducing complications is an important evaluation criterion of efficacy and safety of hypoglycemic drugs. Previous studies have shown that the dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP4i), such as sitagliptin, might reduce the incidence of major cardiovascular events (MACEs). However, the safety and efficacy of sitagliptin remains controversial, especially the safety for cardiovascular related events. Here, a systematic review was conducted to assess the cardiovascular safety of sitagliptin in T2DM patients. The literature research dating up to October 2018 was performed in the electronic database. The clinical trials about sitagliptin for T2DM patients were included. Two reviewers independently screened literature according to the inclusion and exclusion criteria. The primary outcome was the MACE, and the secondary outcome was all-cause mortality. Finally, 32 clinical trials composed of 16082 T2DM patients were included in this meta-analysis. The results showed that: there was no significant difference between sitagliptin group and the control group on MACE (odds ratio (OR) = 0.85, 95% confidence intervals (CIs) = 0.63–1.15), myocardial infarction (MI) (OR = 0.66, 95% CI = 0.38–1.16), stroke (OR = 0.83, 95% CI = 0.44–1.54) and mortality (OR = 0.52, 95% CI = 0.26–1.07). These results demonstrated that sitagliptin did not increase the risk of cardiovascular events in patients with T2DM.

scholarly journals APOPTOTIC PROCESSES’ RESEARCH ON THE MODEL OF TYPE 2 DIABETES MELLITUS ON OBESITY’S BACKGROUND UNDER THE INFLUENCE OF DENSE BEAN EXTRACT

2020 ◽  
Vol 73 (8) ◽  
pp. 1690-1695
Author(s):  
Viktoria A. Rybak ◽  
Viktoria V. Korol ◽  
Natalia V. Derkach
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cell Function ◽  
Male Rats ◽  
Control Group ◽  
Citrate Buffer ◽  
Pancreatic Cell ◽  
Alcoholic Fatty Liver

The aim of the study was to observe the influence of dense bean extract on the intensity of apoptotic processes in the liver cells and pancreas of rats on a model of type 2 diabetes mellitus on obesity’s background. Materials and methods: The main method was to model type 2 diabetes mellitus on the background of obesity in organism of mature six-month-old male rats of the Wistar population (n = 21), weighing 150-170 g. The modelling was carried out by intraperitoneal low dose administration of streptozotocin (30 mg / kg, in citrate buffer pH = 4, 5) inside after three months period of keeping animals on a combined diet. Apoptosis in DNA samples of liver and pancreas cells was identified in duplicates using electrophoresis in a 1% agarose gel with using a 1kb DNA SibEnzyme apoptosis marker (from 10,000 to 250 nucleotides). Results: Only in two of the seven studied DNA samples of the pancreas of a group of rats, treated with a dense bean extract, were observed the traces of necrosis without detectable manifestations of the apoptotic process. It situates at the level of indicators of the animals’ intact control group and indicates the distinct effect’s presence which includes maintaining pancreas cells survival (in both endocrine and exocrine parts) if imbalance of carbohydrate and lipid metabolism take place in organism. Conclusion: Dense bean extract showed a more distinct effect than the comparison drug metformin in relation to the risk of premature loss of pancreatic cell function and the development of non-alcoholic fatty liver disease. A dense bean extract is promising for further pharmacological studies, with the aim of creating phytopreparations – «Glyphasonorm» tablets and «Glyfasolin» capsules for the correction of type 2 diabetes mellitus and its complications.

scholarly journals Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model

2018 ◽  
Vol 52 (2) ◽  
pp. 69-75 ◽  
Author(s):  
Titin Andri Wihastuti ◽  
Teuku Heriansyah ◽  
Hanifa Hanifa ◽  
Sri Andarini ◽  
Zuhrotus Sholichah ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Rat Model ◽  
Foam Cells ◽  
Male Rats ◽  
Sprague Dawley ◽  
Early Stages ◽  
Sprague Dawley Rat

AbstractObjective. Increase in the low-density lipoprotein (LDL) level in diabetes mellitus and atherosclerosis is related to lipoprotein associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids (oxNEFA). LysoPC regulates inflammation mediators, including intra-cellular adhesion molecule-1 (ICAM-1). Darapladib is known as a Lp-PLA2 specific inhibitor. The aim of this study was to reveal the effect of darapladib on the foam cell number, inducible nitric oxide synthase (iNOS), and ICAM-1 expression in aorta at early stages of the atherosclerosis in type 2 diabetes mellitus Sprague-Dawley rat model.Methods. Thirty Sprague-Dawley male rats were divided into 3 main groups: control, rats with type 2 diabetes mellitus (T2DM), and T2DM rats treated with darapladib (T2DM-DP). Each group was divided into 2 subgroups according the time of treatment: 8-week and 16-week treatment group. Fasting blood glucose, insulin resistance, and lipid profile were measured and analyzed to ensure T2DM model. The foam cells number were detected using hematoxylin-eosin (HE) staining and the expression of iNOS and ICAM-1 was analyzed using double immunofluorescence staining.Results. Induction of T2DM in male Sprague-Dawley rats after high fat diet and streptozotocin injection was confirmed by elevated levels of total cholesterol and LDL and increased fasting glucose and insulin levels compared to controls after both times of treatment. Moreover, T2DM in rats induced a significant increase (p<0.05) in the foam cells number and iNOS and ICAM-1 expression in aorta compared to controls after both treatment times. Darapladib treatment significantly reduced (p<0.05) foam cells number as well as iNOS expression in aorta in rats with T2DM after both treatment times. A significant decrease (p<0.05) in ICAM-1 expression in aorta was observed after darapladib treatment in rats with T2DM only after 8 weeks of treatment.Conclusion. Our data indicate that darapladib can decrease the foam cells number, iNOS, and ICAM-1 expression in aorta at the early stages of atherosclerosis in T2DM rat model.

scholarly journals Beneficial Effects of Soygurt Intake in Type 2 Diabetes Mellitus in Animal Model Rat (Rattus Norvegitus)

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Ni Wayan Desi Bintari ◽  
Putu Ayu Parwati
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Blood Sugar ◽  
Blood Sugar Level ◽  
Diabetic Rats ◽  
Male Rats ◽  
Probiotic Food

Type 2 Diabetes Mellitus (T2DM) is the more common type of diabetes results from the ineffective use of insulin. Improvement of the metabolic system in T2DM patients can be done through the regulation of gut microbiota balance. Gut microbial improvement can be modulated directly by probiotic food consumption. Soygurt is probiotic food with a low glycemic index (GI) and glycemic load (GL) value and rich in isoflavones, which has a potential effect in reducing diabetes risk. The aim of this study is to determine the effect of soygurt consumption in blood glucose levels and body weight of albino wistar rats (Rattus norvegitus). Reseach using a completely randomized design for experimental study. Subjects of this research are 30 male rats (R. norvegistus) aged 2-3 months with average body weight 150-200 gr. Diabetic rats were induced by using single intraperitoneal injection (175 mg/kg BW) alloxan monohydrate. Soygurt feeding given once daily using oral gavage feeding. The result showed that soygurt feeding in diabetic rats with three variations of treatment could significantly (p<0,05), lowering blood sugar level and improve body weight after 28 days of treatment. Treatment of 4ml/day soygurt has the highest effect in lowering blood sugar level and improving body weight, followed by treatment of 3ml/day and 2ml/day soygurt.

Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function

2011 ◽  
Vol 301 (6) ◽  
pp. E1220-E1228 ◽  
Author(s):  
Christine Hamann ◽  
Claudia Goettsch ◽  
Jan Mettelsiefen ◽  
Veit Henkenjohann ◽  
Martina Rauner ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Bone Regeneration ◽  
Rat Model ◽  
Diabetic Rats ◽  
Low Bone Mass ◽  
Insulin Resistant ◽  
Zdf Rats

Patients with diabetes mellitus have an impaired bone metabolism; however, the underlying mechanisms are poorly understood. Here, we analyzed the impact of type 2 diabetes mellitus on bone physiology and regeneration using Zucker diabetic fatty (ZDF) rats, an established rat model of insulin-resistant type 2 diabetes mellitus. ZDF rats develop diabetes with vascular complications when fed a Western diet. In 21-wk-old diabetic rats, bone mineral density (BMD) was 22.5% (total) and 54.6% (trabecular) lower at the distal femur and 17.2% (total) and 20.4% (trabecular) lower at the lumbar spine, respectively, compared with nondiabetic animals. BMD distribution measured by backscattered electron imaging postmortem was not different between diabetic and nondiabetic rats, but evaluation of histomorphometric indexes revealed lower mineralized bone volume/tissue volume, trabecular thickness, and trabecular number. Osteoblast differentiation of diabetic rats was impaired based on lower alkaline phosphatase activity (−20%) and mineralized matrix formation (−55%). In addition, the expression of the osteoblast-specific genes bone morphogenetic protein-2, RUNX2, osteocalcin, and osteopontin was reduced by 40–80%. Osteoclast biology was not affected based on tartrate-resistant acidic phosphatase staining, pit formation assay, and gene profiling. To validate the implications of these molecular and cellular findings in a clinically relevant model, a subcritical bone defect of 3 mm was created at the left femur after stabilization with a four-hole plate, and bone regeneration was monitored by X-ray and microcomputed tomography analyses over 12 wk. While nondiabetic rats filled the defects by 57%, diabetic rats showed delayed bone regeneration with only 21% defect filling. In conclusion, we identified suppressed osteoblastogenesis as a cause and mechanism for low bone mass and impaired bone regeneration in a rat model of type 2 diabetes mellitus.

scholarly journals The Hepatoprotective Effect of Jaboticaba Peel Powder in a Rat Model of Type 2 Diabetes Mellitus Involves the Modulation of Thiol/Disulfide Redox State through the Upregulation of Glutathione Synthesis

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Andréia Quatrin ◽  
Lisiane Conte ◽  
Dariane Trivisiol da Silva ◽  
Cassieli Gehlen Figueiredo ◽  
Sabrina Somacal ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Rat Model ◽  
Antioxidant Properties ◽  
Redox Balance ◽  
Diabetic Rats ◽  
Hepatic Damage ◽  
Glutathione Synthesis

Jaboticaba peel powder (JPP) is rich in bioactive compounds, mainly soluble and insoluble polyphenols with great antioxidant properties. The aim of this study is to evaluate the effects of JPP supplementation on the oxidative stress and hepatic damage in a rat model of type 2 diabetes mellitus (T2DM). Diabetic rats received vehicle or JPP at 2.7 (JPP-I), 5.4 (JPP-II), or 10.8 (JPP-III) g/L in drinking water during 8 weeks. JPP-III attenuated hyperglycaemia and dyslipidemia increased by 86% the liver content of nonprotein thiol groups and by 90% the GSH/GSSG ratio by activating glutathione synthesis. Accordingly, JPP supplementation prevented the loss of activity of the sulfhydryl-dependent enzymeδ-aminolaevulinic acid dehydratase and attenuated hepatic injury assessed by the reduction of serum aspartate aminotransferase activity and liver hypertrophy. Our results support that JPP supplementation to T2DM rats decreases hepatic damage most likely by increasing glutathione synthesis and modulating the thiol/disulfide redox balance.

ESTIMATION OF SERUM FERRITIN LEVELS IN TYPE 2 DIABETIC PATIENTS AND ITS RELATION WITH HbA1C LEVEL.

2019 ◽  
Vol 3 (8) ◽  
Author(s):  
Shah Namrata Vinubhai ◽  
Pardeep Agarwal ◽  
Bushra Fiza ◽  
Ramkishan Jat
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Sugar ◽  
Serum Ferritin ◽  
Inflammatory Marker ◽  
Control Group ◽  
Diabetic Patients ◽  
Positive Correlation

Background: Serum ferritin is known as an index for body iron stores also as an inflammatory marker and it is influenced by several disease. We were looking for a correlation between HbA1c and S. Ferritin in type 2 DM. Methodology: The present study a total of 150 participants were enrolled of which 100 were confirmed cases of Type 2 Diabetes Mellitus and rest 50 age and sex matched healthy subjects constituted the control group. All were screened for HbA1c, Fasting blood sugar, Post prandial blood sugar and S.Ferritin. Results: A highly significant variation and positive correlation was observed with respect to S.Ferritin and HbA1c levels. Mean S.Ferritin was high in the subgroup with poor glycemic control. Conclusion: The fasting, post prandial sugar levels, HbA1c and S.Ferritin were significantly higher in the diabetic subjects. This study shows a positive correlation between HbA1c and S. Ferritin levels. So we can conclude that in diabetic patients S. Ferritin may serve as an independent marker of poor glycemic and metabolic control. Keywords: Serum ferritin, Type 2 Diabetes Mellitus, HbA1c.

Rheumatoid Factor in Type 2 Male Diabetes Mellitus Patients in a Tertiary Care Hospital of Bangladesh

2018 ◽  
Vol 4 (2) ◽  
pp. 58-62
Author(s):  
Roksana Yeasmin ◽  
MA Muttalib ◽  
Kazi Nazneen Sultana ◽  
Nizamul Hoque Bhuiyan ◽  
Md Jamil Hasan Karami ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Uric Acid ◽  
Rheumatoid Factor ◽  
Serum Uric Acid ◽  
Control Group ◽  
Healthy Male ◽  
Male Patients

Background: Type 2 diabetes mellitus is a chronic disease characterized by relative or absolute deficiency of insulin, resulting in glucose intolerance.Objectives: The present study was planned to see the associations of serum uric acid with positive Rheumatoid factor in type 2 male diabetes mellitus patients. Methodology: This case control study was carried out at the department of Biochemistry at Ibrahim Medical College, Dhaka, Bangladesh. The duration of the study was from June 2015 to June 2016 for a period of one year. In this present study, male patients with type 2 diabetes mellitus were taken as case group and age and sex matched healthy male were taken as control group. Rheumatoid factor was measured from the blood of all case and control group respondents. Others blood para meters were also measured for the correlation with the diabetes mellitus patients.Results: In this present study, 110 male patients presented with type 2 diabetes mellitus were recruited as case and age and sex matched healthy male were recruited as control. More rheumatoid factor positive in type 2 DM male patients with the uric acid range between 6.5 to 9.5 mg/dL. The number of patients was 5 out of total 9 rheumatoid factor positive cases. In this study serum uric acid was significantly correlated with rheumatoid factor in type 2 male diabetic patients. Rheumatoid factor positive cases were taking insulin among 9 and it was statistically significantly associated (p<0.001). Conclusion: In this study serum uric acid is significantly associated with positive rheumatoid factor in type 2 male diabetic patients.Journal of Current and Advance Medical Research 2017;4(2):58-62

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