Pharmacotherapy with Thymoquinone Improved Pancreatic β-Cell Integrity and Functional Activity, Enhanced Islets Revascularization, and Alleviated Metabolic and Hepato-Renal Disturbances in Streptozotocin-Induced Diabetes in Rats

Pharmacology ◽  
2017 ◽  
Vol 101 (1-2) ◽  
pp. 9-21 ◽  
Author(s):  
Adel Galal El-Shemi ◽  
Osama Adnan Kensara ◽  
Aiman Alsaegh ◽  
Mohammed Hasan Mukhtar
Keyword(s):  
Lipid Profile ◽  
Caspase 3 ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Β Cells ◽  
Insulin Homeostasis

Aims: This study is aimed at evaluating the antidiabetic effects of thymoquinone (TQ) on streptozotocin (STZ)-induced diabetes in rats, and exploring the possible underlying mechanisms. Methods: Diabetes was induced in adult male Wistar rats by intraperitoneal injection of freshly prepared STZ (65 mg/kg). After disease induction, 42 rats were equally assigned to: controls, STZ-diabetic group, and STZ-diabetic group treated with oral TQ (35 mg/kg/day) for 5 weeks. Fasting blood glucose levels were determined weekly, and the animals were euthanized at day 38 post-STZ injection. Blood samples were assessed for glucose-insulin homeostasis parameters (plasma glucose, glycated hemoglobin, serum insulin, homeostatic model assessment of insulin resistance, and insulin sensitivity index) and lipid profile. Resected pancreases were subjected to histological examination and immunohistochemical or enzyme-linked immunosorbent assay assessment to determine the pancreatic expression of insulin sensitizing β-cells, anti-apoptotic protein “survivin,” apoptosis-inducer “caspase-3,” prototypic angiogenic factors (vascular endothelial growth factor [VEGF] and endothelial cluster of differentiation 31 [CD31]), pro- and anti-inflammatory cytokines (interleukin-1beta [IL-1β] and interleukin-10 [IL-10], respectively), thiobarbituric acid reactive substances (TBARS), total glutathione (GSH), and superoxide dismutase (SOD). The hepato-renal statuses were assessed biochemically and histologically. Results: Therapy with TQ markedly improved the integrity of pancreatic islets, glucose-insulin homeostasis-related parameters, lipid profile parameters, and hepato-renal functional and histomorphological statuses that collectively were severely deteriorated in untreated diabetic group. Mechanistically, TQ therapy efficiently increased insulin producing β-cells, upregulated survivin, VEGF, CD31, IL-10, GSH and SOD, and downregulated caspase-3, IL-1β, and TBARSs in the pancreatic tissues of STZ-diabetic rats. Conclusions: These findings prove the anti-diabetic potential of TQ and its efficacy in regenerating pancreatic β-cells and ameliorating pancreatic inflammation and oxidative stress, and highlight its novelty in repressing apoptosis of β-cells and enhancing islet revascularization in STZ-diabetic rats. Further studies are required to support these findings and realize their possible clinical significance.

scholarly journals Black Seed Thymoquinone Improved Insulin Secretion, Hepatic Glycogen Storage, and Oxidative Stress in Streptozotocin-Induced Diabetic Male Wistar Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Heba M. A. Abdelrazek ◽  
Omnia E. Kilany ◽  
Muhammad A. A. Muhammad ◽  
Hend M. Tag ◽  
Aaser M. Abdelazim
Keyword(s):  
Lipid Profile ◽  
Pancreatic Islet ◽  
Wistar Rats ◽  
Nigella Sativa ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Hepatic Glycogen ◽  
Therapeutic Effects ◽  
Male Wistar Rats

Diabetes mellitus is one of the metabolic diseases having several complications. Nigella sativa oil (NSO) might have beneficial effects in the treatment of diabetic complications. Thirty-two mature male Wistar rats were equally divided into four experimental groups: control, control NSO 2 mL/kg, streptozotocin- (STZ-) induced diabetic, and diabetic (STZ-induced) treated with oral NSO 2 mg/kg for 30 days. Fasting blood glucose (FBG), insulin, and lipid profile levels were determined. Pancreatic and hepatic tissues were used for catalase and GSH. Histopathology, hepatic glycogen contents, insulin immunohistochemistry, and pancreatic islet morphometry were performed. NSO 2 mL/kg was noticed to decrease (P<0.05) FBG and increase (P<0.05) insulin levels in diabetic rats than in diabetic nontreated animals. Lipid profile showed significant (P<0.5) improvement in diabetic rats that received NSO 2 mL/kg than in the diabetic group. Both pancreatic and hepatic catalase and GSH activities revealed a significant (P<0.05) increment in the diabetic group treated with NSO than in the diabetic animals. NSO improved the histopathological picture and hepatic glycogen contents of the diabetic group as well as increased (P<0.05) insulin immunoreactive parts % and mean pancreatic islet diameter. NSO exerts ameliorative and therapeutic effects on the STZ-induced diabetic male Wistar rats.

scholarly journals Polysaccharides fromEnteromorpha proliferaImprove Glucose Metabolism in Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Wenting Lin ◽  
Wenxiang Wang ◽  
Dongdong Liao ◽  
Damiao Chen ◽  
Pingping Zhu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Mrna Expression ◽  
Glucose Transporter ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
High Dose ◽  
Sensitivity Index ◽  
Serum Samples ◽  
Glut 4

This study investigated the effects of polysaccharides fromEnteromorpha prolifera(PEP) on glucose metabolism in a rat model of diabetes mellitus (DM). PEP (0, 150, 300, and 600 mg/kg) was administered intragastrically to rats for four weeks. After treatment, fasting blood glucose (FBG) and insulin (INS) levels were measured, and the insulin sensitivity index (ISI) was calculated. The morphopathological changes in the pancreas were observed. Serum samples were collected to measure the oxidant-antioxidant status. The mRNA expression levels of glucokinase (GCK) and insulin receptor (InsR) in liver tissue and glucose transporter type 4 (GLUT-4) and adiponectin (APN) in adipose tissue were determined. Compared with the model group, the FBG and INS levels were lower, the ISI was higher, and the number of isletβ-cells was significantly increased in all the PEP groups. In the medium- and high-dose PEP groups, MDA levels decreased, and the enzymatic activities of SOD and GSH-Px increased. The mRNA expression of InsR and GCK increased in all the PEP groups; APN mRNA expression increased in the high-dose PEP group, and GLUT-4 mRNA expression increased in adipose tissue. These findings suggest that PEP is a potential therapeutic agent that can be utilized to treat DM.

scholarly journals Anti-Hyperglycemic and Anti-Inflammatory Activities of Polyphenolic-Rich Extract of Syzygium cumini Linn Leaves in Alloxan-Induced Diabetic Rats

2018 ◽  
Vol 23 ◽  
pp. 2515690X1877063 ◽  
Author(s):  
Basiru O. Ajiboye ◽  
Oluwafemi A. Ojo ◽  
Olivia S. Akuboh ◽  
Okesola M. Abiola ◽  
Olajumoke Idowu ◽  
...  
Keyword(s):  
Glucose Transporter ◽  
Glycated Hemoglobin ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Model Assessment ◽  
Syzygium Cumini ◽  
Homeostasis Model Assessment ◽  
Free Phenol ◽  
Female Wistar Rats ◽  
Anti Inflammatory

In this study, anti-hyperglycemic and anti-inflammatory activities of polyphenolic-rich extract of Syzygium cumini leaves in alloxan-induced diabetic rats were determined. Diabetes was induced by a single intraperitoneal injection of alloxan (150 mg/kg body weight) in female Wistar rats. The rats were orally administered with 400 mg/kg free phenol, 400 mg/kg bound phenol, and 5 mg/kg metformin, respectively. On the 14th day of oral administration, the animals were sacrificed, anti-hyperglycemic and anti-inflammatory were assessed. Fasting blood glucose and glycated hemoglobin levels; homeostasis model assessment–insulin resistance scores, lipid peroxidation concentration, glucose-6-phosphatase activity, and all concentrations of anti-inflammatory studied in alloxan-induced diabetic rats were significantly ( P < .05) reduced with the administration of polyphenolic-rich extract of Syzygium cumini leaves. Also there was significant ( P < .05) increase in glycogen and insulin concentrations, pancreatic β-cell scores, antioxidant enzymes and hexokinase activities, as well as glucose transporter levels in diabetic animals administered with polyphenolic-rich extract of S cumini leaves. The results indicate that S cumini leaves possess anti-hyperglycemic and anti-inflammatory activities.

Antidiabetic and antioxidative properties of the hydro-methanolic extract (60:40) of rhizomes of Curcuma amada roxb. (Zingiberaceae) in streptozotocin-induced diabetic male albino rat: a dose-dependent study through biochemical and genomic approaches

2019 ◽  
Vol 16 (4) ◽  
Author(s):  
Dipanwita Mitra ◽  
Riya Sarkar ◽  
Debidas Ghosh
Keyword(s):  
Body Weight ◽  
Methanolic Extract ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Dependent Manner ◽  
Male Adult ◽  
Curcuma Amada ◽  
Corrective Effect ◽  
Dose Dependent

Abstract Background Curcuma amada is the most popular traditional medicine in India for the treatment of diabetes. The present study aimed to focus the antidiabetic and antioxidative activity of C. amada through the analysis of biochemical and genomic levels in a dose-dependent manner in streptozotocin-induced male adult rat. Method Streptozotocin-induced diabetic rats were administered orally with hydro-methanolic extract of C. amada at the dose of 10, 20, 40 and 80 mg/100 g body weight of rats for 28 days. The antidiabetic and antioxidative efficacy of the extract on glycemic, enzymatic, genomic and histological sensors along with toxicity study was investigated. Results The result showed a significant antidiabetic and antioxidative effect of the extract at dose-dependent manner. The significant recovery of fasting blood glucose level, serum insulin, activity of carbohydrate metabolic enzymes and antioxidative enzymes in extract-treated diabetic group as compared to untreated diabetic group were noted. After the extract treatment, the size of pancreatic islet and cell population densities were significantly increased. Activities of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase in liver were significantly recovered along with the correction of Bax and Bcl-2 gene expression in hepatic tissue after the extract treatment in diabetic rats in respect to untreated diabetic group. Out of all the doses, the significant effects were noted at the dose of 20 mg/100 g body weight which has been considered as threshold dose in the concern. Conclusion It may be concluded that the significant and corrective effect in most of the sensors was noted at the minimum dose of 20 mg/100 g body weight of hydro-methanolic extract of C. amada without producing any toxicity.

scholarly journals The Effect of Tianmai Xiaoke Pian on Insulin Resistance through PI3-K/AKT Signal Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Nana Wang ◽  
Tiegang Li ◽  
Ping Han
Keyword(s):  
Insulin Resistance ◽  
Fasting Blood Glucose ◽  
Area Under The Curve ◽  
Diabetic Rats ◽  
Signal Pathway ◽  
Chromium Picolinate ◽  
Oral Glucose ◽  
Model Assessment ◽  
Insulin Sensitizer ◽  
Type 2 Diabetic Mellitus

In the clinical setting, given the potential adverse effects of thiazolidinediones and biguanides, we often have difficulty in treatment that no other insulin sensitizers are available for use in type 2 diabetic mellitus (T2DM) patients. Tianmai Xiaoke Pian (TMXKP) is a traditional Chinese medicine tablet, which is comprised of chromium picolinate, Tianhuafen, Maidong, and Wuweizi. To understand its mechanism of action on insulin resistance, TMXKP (50 mg/kg orally) was tested in T2DM rats (induced by a high-fat diet and streptozotocin). Eight weeks later, fasting blood glucose (FBG) and oral glucose tolerance tests (OGTT) were performed. Area under the curve (AUC) and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated, and PI3-K/AKT signal pathway-related genes and proteins were tested by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis in muscle, adipose, and liver tissues, respectively. TMXKP significantly reduced FBG, OGTT, AUC, and HOMA-IR in diabetic ratsP<0.05. Furthermore, we also observed that TMXKP could significantly decreaseIRS-1,IRS-2,PI3-K p85α, andAKT2gene expression and also IRS-1, IRS-2, PI3-K, AKT2, and p-AKT2 protein expression levelsP<0.05in diabetic rats. These findings confirm that TMXKP can alleviate insulin resistance in T2DM rats through the PI3K/AKT pathway. Thus TMXKP appears to be a promising insulin sensitizer.

scholarly journals VMP1-related autophagy induced by a fructose-rich diet in β-cells: its prevention by incretins

2017 ◽  
Vol 131 (8) ◽  
pp. 673-687 ◽  
Author(s):  
Bárbara Maiztegui ◽  
Verónica Boggio ◽  
Carolina L. Román ◽  
Luis E. Flores ◽  
Héctor Del Zotto ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Cell Function ◽  
Cell Damage ◽  
Cell Mass ◽  
Ultrastructural Changes ◽  
Mrna Levels ◽  
Model Assessment ◽  
Β Cells ◽  
Β Cell ◽  
Insulin Mrna

The aim of the present study was to demonstrate the role of autophagy and incretins in the fructose-induced alteration of β-cell mass and function. Normal Wistar rats were fed (3 weeks) with a commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin-4 (CE and FE). Serum levels of metabolic/endocrine parameters, β-cell mass, morphology/ultrastructure and apoptosis, vacuole membrane protein 1 (VMP1) expression and glucose-stimulated insulin secretion (GSIS) were studied. Complementary to this, islets isolated from normal rats were cultured (3 days) without (C) or with F and F + exendin-4 or chloroquine. Expression of autophagy-related proteins [VMP1 and microtubule-associated protein light chain 3 (LC3)], apoptotic/antiapoptotic markers (caspase-3 and Bcl-2), GSIS and insulin mRNA levels were measured. F rats developed impaired glucose tolerance (IGT) and a significant increase in plasma triacylglycerols, thiobarbituric acid-reactive substances, insulin levels, homoeostasis model assessment (HOMA) for insulin resistance (HOMA-IR) and β-cell function (HOMA-β) indices. A significant reduction in β-cell mass was associated with an increased apoptotic rate and morphological/ultrastructural changes indicative of autophagic activity. All these changes were prevented by either sitagliptin or exendin-4. In cultured islets, F significantly enhanced insulin mRNA and GSIS, decreased Bcl-2 mRNA levels and increased caspase-3 expression. Chloroquine reduced these changes, suggesting the participation of autophagy in this process. Indeed, F induced the increase of both VMP1 expression and LC3-II, suggesting that VMP1-related autophagy is activated in injured β-cells. Exendin-4 prevented islet-cell damage and autophagy development. VMP1-related autophagy is a reactive process against F-induced islet dysfunction, being prevented by exendin-4 treatment. This knowledge could help in the use of autophagy as a potential target for preventing progression from IGT to type 2 diabetes mellitus.

scholarly journals Serum concentrations of asprosin in new-onset type 2 diabetes

2020 ◽  
Author(s):  
Shakiba Naiemian ◽  
Mohsen naeemipour ◽  
Mehdi Zarei ◽  
Ali Gohari ◽  
Mohammad Reza Behroozikhah ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fasting Blood Glucose ◽  
Density Lipoprotein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Model Assessment ◽  
Serum Concentrations ◽  
Atherosclerotic Risk Factor

Abstract Background: Asprosin, a newly identified adipokine, is pathologically increased in individuals with insulin resistance. However, the available evidence on the association of asprosin and type 2 diabetes mellitus (T2DM) status is still scarce. Therefore, this study aimed to determine the relationship between serum concentrations of asprosin and T2DM status . Methods: This observational study was performed based on 194 adults (97 newly diagnosed T2DM and 97 healthy individuals). Anthropometric and biochemical variables were determined in all participants . Serum concentrations of asprosin were measured using enzyme-linked immunosorbent assay (ELISA). Results: In patients with T2DM, the serum concentrations of asprosin were significantly higher than the healthy controls (4.18 [IQR: 4.4] vs. 3.5 [IQR: 1.85], P< 0.001). The concentrations of asprosin were significantly correlated with body mass index (BMI) and fasting blood glucose (FBG) in healthy subjects and with BMI, FBG, hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), and quantitative insulin check index (QUICKI), triacylglycerol (TAG) and total cholesterol/ high-density lipoprotein cholesterol (TC/HDL-C) ratio in the T2DM group. In fully adjusted model, the odds ratio (OR) of T2DM with serum concentrations of asprosin was approximately 1.547 (95% CI 1.293-1.850, P< 0.001) compared to the control group . Multiple stepwise regression analysis indicated that FBG and HOMA-IR were independently associated with asprosin in T2DM. Conclusion : Our findings indicated that serum concentrations of asprosin are increased in patients with T2DM. Also, asprosin is correlated with insulin resistance and TC/HDL-C ratio (atherosclerotic risk factor of cardiovascular diseases) in patients with T2DM.

scholarly journals Effect of Sago Analog Rice and Red Bean Diet to β Cells Pancreas Refinement in STZ-NA Induced Diabetic Rats

2020 ◽  
pp. 667-673
Author(s):  
Sri Budi Wahjuningsih ◽  
Haslina Haslina ◽  
Agus Tri Putranto ◽  
Mita Nurul Azkia
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Insulin Level ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Red Bean

The study aims to determine the effect of sago analogue rice and red beans in diabetic rats to repair pancreatic β-cells. Thirty-five males Wistar rats were divided into 5 groups: normal group diet (STD), the diabetic group (STDD) with a standard feed diet, the diabetic group with mentik wangi rice (MWRD), the diabetic group with sago analogue rice (SARD) and the diabetic group with sago analogue rice with the addition of 10% red bean flour (SARKBD). All groups were analysed for dietary interventions, blood glucose level, insulin level for HOMA-β and HOMA S indices and measurement of insulin level by using IHC analysis. In addition, short-chain fatty acids (SCFA) analysis was performed in the caecum. This study showed that decreasing blood glucose level shown in SARD and RASKBD groups. The pancreatic β-cell number indicated an increase in the SARD group compares to the STDD group. The pool total of SCFA in SARD group was the highest among of all groups, as well as the acetate, propionate and butyrate pools. These results indicate that the sago analogue rice diet could repair and increase the expression of pancreatic β-cell through absorption inhibition mechanisms and by increasing insulin sensitivity and the SCFA level.

scholarly journals Assessment on Functionality and Viability of β cells Following Repetitive Dosage Administration of Ethanolic Extracts of Andrographis paniculata on Streptozotocin-induced Diabetic Rats

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Abdul Razak K ◽  
Mariam A ◽  
Amirin S ◽  
Mohd Zaini A
Keyword(s):  
Blood Glucose ◽  
Plant Extracts ◽  
Fasting Blood Glucose ◽  
Insulin Level ◽  
Diabetic Rats ◽  
Andrographis Paniculata ◽  
Β Cells ◽  
Glucose Levels ◽  
Ethanolic Extracts ◽  
Before And After

Introduction: The study was done at the aim to assess the functionality and viability of the β cells of the streptozotocin-induced diabetic rats model following repetitive dosage of administration of ethanolic extracts of Andrographis paniculata. Materials and Methods: The diabetic rats were treated with the extracts for fourteen days and at the dose given was 500 mg/kg twice daily. The assessments were made on fasting blood glucose, insulin, and immunohistochemical aspect of β cells before and after treatment. Results: The results showed that there was a significant reduction on fasting blood glucose levels in metformin, 95% and 50% ethanolic plant extracts-treated groups but on insulin level only 95% and 50% ethanolic extracts-treated groups gave a significant reduction (p<0.05). Immunohistochemical assessments revealed that all extract groups and metformin-treated were significantly increased in the population of β cells (p<0.01). Conclusion: This study revealed that the plant extracts showed an ability to promote the growth or rejuvenate the STZdestructed β cells and in turn lower the blood glucose level.

scholarly journals Effects of goat milk kefir fortified with vitamin D3 on Interleukin-18 levels in diabetic rats

Food Research ◽  
2020 ◽  
Vol 4 (S3) ◽  
pp. 197-201
Author(s):  
K.D. Anggraeni ◽  
G. Anjani ◽  
M. Ardiaria ◽  
C. Nissa ◽  
S.Y. Huang ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Vitamin D3 ◽  
Fasting Blood Glucose ◽  
Goat Milk ◽  
Positive Control ◽  
Negative Control ◽  
Diabetic Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Control Group Design

Hyperglycemia causes increased oxidative stress through an imbalance of reactive oxygen species and antioxidative mechanisms. It stimulates the production of inflammatory mediators and cytokines such as TNF-α, interleukin (IL)-1, and IL-18. Goat milk kefir and vitamin D3 have potential as antioxidants and anti-inflammatory agents that can repair damage to pancreatic β cells. This study analyzed the effects of goat milk kefir fortified with vitamin D3 on the IL-18 level in diabetic rats. An experimental randomized pre-post test with control group design was conducted on 20 male Wistar rats divided into four groups, namely negative control (K-), positive control (K+), treatment with unfortified kefir (P1), and treatment with kefir fortified with vitamin D3. The intervention lasted 34 days. Fasting blood glucose and IL-18 levels were measured before and after intervention. Blood glucose and IL-18 levels were analyzed using the glucose oxidase p-aminophenol method and enzyme-linked immunosorbent assay, respectively. No significant increase in the IL-18 level was found in the P1 group with a median of 56.5 (10–252.7) pg/mL to 148.2 (106.8–428.3) pg/mL (p = 0.465) or P2 group with a median of 117.3 (91.8–146.8) pg/mL to 246.7 (168.8–311) pg/mL (p = 0.068), and no significant increase was observed in blood glucose levels in the P1 group (366.9±134.8 mg/dL to 462.1±156.9 mg/dL, p = 0.357) or P2 group (415.0±203.8 mg/dL to 258±129 mg/dL, p = 0.463). Goat milk kefir fortified with vitamin D3 could maintain blood glucose and IL-18 levels.

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