Glibenclamide Group Research Articles

Influence of silymarin and chromium picolinate on the pharmacotherapy of rats with induced diabetes

Food supplements are easily acquired and used in various countries. Silymarin has been indicated for diseases of the liver and Chromium picolinate has been indicated for body weight loss and for the improvement of glycemic index. The objective of the present study was to assess the effects of short-term treatment with a combination of silymarin (50 mg/kg) and chromium picolinate (5 µg/kg) on the standard glibenclamide treatment (10 mg/kg) of rats with induced diabetes. DM2 was induced with streptozotocin. Experimental groups of rats: healthy control group, glibenclamide diabetic group, silymarin diabetic group, and silymarin, chromium picolinate and glibenclamide group. After 10 days of oral treatment, we determined body weight, fasting glycemia, glycemia 1 h after gastric gavage with sucrose, and AST and ALT transaminases. Statistical analysis of the data indicated that there was no change in body weight or fasting glycemia, but that glycemia increased after gavage with sucrose in the group submitted to combined therapy. Thus, we concluded that the combination of silymarin and chromium picolinate reduced the efficacy of glibenclamide in the short term, although the two substances had a protective effect on the liver as observed by the reduction of blood transaminase levels.

The Black Truffle, Tuber melanosporum (Ascomycetes), Ameliorates Hyperglycemia and Regulates Insulin Signaling Pathway in STZ-Induced Diabetic Rats.

Black truffle mushroom, Tuber melanosporum, is effective in treating various symptoms associated with diabetes mellitus such as hyperglycemia, oxidative stress, and hyperlipidemia and is used as traditional medicine. The aim of our study is to elucidate the antidiabetic potential of T. melanosporum. Male albino Wistar rats were administered a single dose of STZ (40 mg/kg b.w.) to induce mild diabetes mellitus (DM). After the confirmation of hyperglycemia, rats were treated with three different doses of truffle extract (TE) (200, 400, and 600 mg/kg b.w.) for the duration of 45 days. The various tissues were collected at the end of the study. The levels of glucose, oral glucose tolerance test, insulin, hexokinase, glucose 6 phosphatase, and fructose-1,6-bisphosphatase, and regulation of insulin signaling genes were quantified. The results showed that STZ- induced rats have a higher blood glucose level and a lower insulin level compared with the control groups and TE treated groups. Results also reveal that STZ suppressed the expressions of insulin signaling genes in diabetic rats and TE treatment resulted in a positive regulation of the insulin signaling pathway. The results of TE are similar to the results attained in glibenclamide (GB) group rats. Overall, the study provides scientific evidence for the medicinal properties of black truffle; future clinical studies can warrant a potential antidiabetic drug in the form of diet.

Gynura divaricataEffect on Blood Glucose Levels in Alloxan-Induced Diabetes Mice

Gynura divaricata (GD) also known as Dewa leaf is one of the Indonesian medicinal plants which are also native to India, Thailand and China. GD is widely used as antidiabetic, antihypertensive and other diseases including several tumors. However, research on the effects of GD as antidiabetic is still not widely practiced, especially in Indonesia. The aim of this research is to investigate the effect of GD ethanolic extract on blood glucose levels of alloxan-induced diabetes mice. This research is an experimental research with pre- and post-test design using 24 male DDY strain mice. Animals experiment is divided into four groups, that are one normal group and three alloxan-induced diabetes mice group that give 1% CMC (control), 400[Formula: see text]mg/kg GD ethanolic extract and 0.65[Formula: see text]mg/kg glibenclamide, respectively. Treatment was given for 14 days. Blood glucose levels were measured before and after inducing alloxan, and after 14 days treatment. At the end of study, all of animals experiment were sacrificed for histological examination. Phytochemical analysis revealed that polyphenols, flavonoids, steroids, triterpenoids, terpenoids and and quinones were present in ethanol extract of GD. The results of this study showed significant ([Formula: see text]) decrease of blood glucose levels after GD ethanolic extract and glibenclamide treatment. The results of histological examination showed improvement in pancreas damage and significant increase in the number of beta cells in GD and glibenclamide groups. The results indicate that dewa leaf ethanolic extract has antidiabetic activity and the effectiveness is the same as glibenclamide. GD also could repair damage of pancreas caused by alloxan induction.

Pharmacological Evaluation of Antidiabetic and Diuretic Activity of Hydro-alcoholic Extract of Anogeissus latifolia Bark

The objective of the present investigation was to study the antidiabetic and diuretic potential of Anogeissus latifolia (A. latifolia) bark in experimental rats. The A. latifolia bark was extracted with hydro-alcoholic solvent by cold extraction method. Acute toxicity study was performed according to OECD 425 guidelines for hydro-alcoholic extracts of A. latifolia bark (ALBE). The dose of 150 mg/kg p.o. and 300 mg/kg, p.o. of ALBE was selected for further studies. Animals were prepared diabetic by administration of alloxan (120 mg/kg, i.p.). The albino rats were divided in to five groups for oral glucose tolerance test (OGTT) and alloxan induced anti diabetic model with six animals in each group. Diabetic animals were treated with hydro-alcoholic extract of A. latifolia bark for 20 days. The blood glucose level was estimated according to standard procedures. Diuretic activity hydro-alcoholic extracts of A. latifolia was evaluated by Lipshitz method. The result shows that hydro-alcoholic extract from bark of Anogeissus latifolia 300 mg/kg (ALBE-II) shown significant hypoglycemic activity as compared to glibenclamide and diabetic group. The ALBE does not exhibit significant diuretic activity which is considered as positive marker in diabetic phenomena. Hence in present study extract of A. latifolia posses antidiabetic activity. This study may be benchmark in future to use of this drug scientifically.

The role of activation of KАTP channels on hydrogen sulfide induced renoprotective effect on diabetic nephropathy.

This work aims to investigate the renal effect of hydrogen sulfide (H2 S), in the experimentally induced diabetic nephropathy, besides the role of activation of АТP-sensitive potassium (KАTP ) channel in that effect. Thirty-two adult male albino rats randomly divided into four groups: Control, streptozotocin-induced diabetic (diabetic nephropathy [DN]), DN+NaHS (the H2 S inducer), and DN+NaHS+Glibenclamide (a selective KАTP channel blocker) groups. Results showed that kidney functions in the diabetic group improved by NaHS proved by the significant decrease in the measured renal injury markers when compared with the diabetic group with an obvious role of inflammation and oxidative stress. However, the improved kidney functions produced by NaHS was reduced by the combination with Glibenclamide. Glibenclamide combination led also to a significant increase in renal total antioxidant capacity, in addition to a significant decrease in renal total nitric oxide (NO) level. Аccordingly, the results from the present work revealed that the renoprotective effects of H2 S in the case of DN through its effects on renal tissue antioxidants and NO can be partially dependent on activation of KАTP channels, while its effect on renal tissue proinflammatory cytokines is independent of it.

Hypoglycemic and Toxic Effect of Morus mesozygia Leaf Extract on the Liver and Kidneys of Alloxan-Induced Hyperglycemic Wistar Rats.

Purpose We investigated the hypoglycemic and toxic effect of Morus mesozygia leaf extract on the liver and kidneys of alloxan-induced hyperglycemic wistar rats. Method Phytochemical analysis was done. Diabetes was induced by the use of alloxan monohydrate in six groups of rats, i.e., 200 mg/kg, 400 mg/kg, 800 mg/kg, glibenclamide, normal saline, and normal control group. Blood glucose was measured at the time of inoculation, then at 1, 2, 3, and 4 hours after. After 14 days, rats were killed under anesthesia; blood collected for measurement of total protein, albumin, TAGs, cholesterol, AST, ALT, urea, and creatinine; and whole tissue of liver and kidneys used for histological studies. Results The extract possessed antidiabetic effects between 400 mg/kg and 800 mg/kg doses, which we attributed to the presence of flavonoids, tannins, terpenoids, and amino acids. There was a drop in total protein and albumin with no statistical significance (P ≥ 0.05). The changes in levels of ALT, TAGs, cholesterol, AST, creatinine, and urea were not statistically different from the standard diabetic drug. The extract was protective against histological damage as there were no significant lesions suggestive of toxicities in the liver and kidneys at doses below 800 mg/kg. Conclusion We established credible evidence that Morus mesozygia leaf extract has hypoglycemic effects between 400 mg/kg and 800 mg/kg and that it is safe on the liver and kidneys of wistar rats at doses less than 800 mg/kg.

Saxagliptin attenuates glomerular podocyte injury by increasing the expression of renal nephrin and podocin in type 2 diabetic rats.

To observe the effects of saxagliptin on the expression of mitogen-activated protein kinase 38 (p38MAPK), nephrin and podocin in renal tissue in type 2 diabetic (T2DM) rats, and to explore the possible mechanism of its renal protection. Forty-eight male Sprague-Dawley rats were used for the study and divided into four different groups: normal controls (Group NC), DM controls (Group DM), DM + glibenclamide (Group Su) and DM + saxagliptin (Group Sa). The day drug administration started was defined as week 0. After 12weeks, hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), urea nitrogen (BUN) and creatinine (Cr) in serum were detected, simultaneously albumin and creatinine in urine were measured, respectively, and then urinary albumin/creatinine ratio (UACR) was calculated. The pathological morphology of kidney tissue in different groups was observed, and the expression of nephrin and podocin mRNA and protein in kidney tissue were detected. (1) After 12weeks, FBG and HbA1c in Group Su and Group Sa were significantly lower than those in Group DM (both P < 0.05), while there was no significant difference between Group Su and Group Sa. TC, TG and UACR in Group Sa were significantly decreased thanthose in Group DM. (2) When compared with Group DM, the kidney weight/body weight ratios, the average width of glomerular basement membrane and foot process fusion ratio were all improved in Group Sa after 12weeks. (3) The expression of p38MAPK mRNA and protein was significantly decreased, while nephrin and podocin mRNA and protein were significantly higher in Group Sa than those in Group DM after 12weeks. (4) A significant negative correlation was detected between p38MAPK mRNA and nephrin (r = - 0.421, P = 0.009) and podocin mRNA (r = - 0.570, P = 0.000), respectively. Saxagliptin can reduce urinary albumin excretion and exert renal protective effect, especially on podocytes in T2DM rats. The mechanism may be related to its inhibition of renal p38MAPK signaling pathway and the increase in the expression of nephrin and podocin in renal tissue, which is independent of its hypoglycemic effect.

Antidiabetic and Antioxidant Effects of the Polyherbal Drug Glucoblock and Glibenclamide in Type 2 Diabetic Rats

The increased prevalence of diabetes, and the huge disease burden on patients has led to an increase in the use of complementary and alternative medicine in diabetes treatment and management.&#x0D; Aim: This study evaluates the antidiabetic and antioxidant effects of the polyherbal capsule glucoblock and glibenclamide in type 2 diabetic rats.&#x0D; Methodology: A total of 35 male Wistar albino rats weighing between 120-220 g were used for this study. The rats were placed on high fat diet, and diabetes induced by a single intraperitoneal injection of freshly prepared streptozotocin (STZ) (45 mg/kg body Wt). Fasting plasma glucose (FPG) was determined using the glucose oxidase method. Fasting plasma insulin (FPI), total oxidant status (TOS), total antioxidant status (TAS) and superoxide dismutase (SOD) levels were quantitatively determined by a rat-specific sandwich-enzyme linked immunosorbent assay (ELISA) method. Insulin resistance (IR) was determined using the homeostatic model assessment of insulin resistance (HOMA-IR) method. Oxidative stress index (OSI) was determined by the ratio of TOS to TAS. Phytochemical analysis was also done on the herbal capsule.&#x0D; Results: Mean FPG levels were significantly lower (p˂0.05) in all groups, compared to the diabetic control. Mean FPG level was significantly higher (p˂0.05) in the combination group, but showed no significant difference (p&gt;0.05) in the glibenclamide group, and glucoblock group, compared to the negative control. HOMA-IR was significantly higher (p&lt;0.05) in the diabetic control compared to the negative control and treatment groups. The combination group had significantly higher (p˂0.05) HOMA-IR values, whereas the individual treatment groups showed no significant difference (p&gt;0.05) when compared to the negative control. TOS was significantly higher (p&lt;0.05) in the diabetic control compared to the negative control and treatment groups. The treatment groups showed no significant difference (p&gt;0.05) in TOS, compared to the negative control. There was significantly lower (p˂0.05) TAS levels in the diabetic and treatment groups, compared to the negative control. OSI values were significantly lower (p˂0.05) in all groups when compared to the diabetic control. Also, OSI values were significantly higher (p˂0.05) in the treatment groups compared to the negative control. SOD was significantly lower (p&lt;0.05) in the diabetic control compared to the negative control and treatment groups. The treatment groups showed no significant difference (p&gt;0.05) in SOD levels, compared to the negative control.&#x0D; Conclusion: Increase in total oxidant status and oxidative stress depleted antioxidant parameters. The polyherbal capsule glucoblock was effective when used alone and produced equipotent effect to the treatment with glibenclamide. However, the combination treatment did not fare better. Antioxidant therapy should be used together with antidiabetics in the management of diabetes, and care should be taken in the use herb-drug combinations.

Effect of Hydrogen Sulfide on the Mitogen-Activated Protein Kinase Signaling Pathway in Cultured Skin Macrophages of Burned Rats

BackgroundThis study aims to investigate the effect of hydrogen sulfide on the mitogen-activated protein kinases signaling pathway in in vitro cultured skin macrophages of burned rats. Materials and methodsThirteen healthy Sprague–Dawley rats were divided into five groups: normal control group, burned control group, sodium hydrogen sulfide group, glibenclamide group, and sodium hydrogen sulfide + glibenclamide group. The burned rats were made into a deep II° 5% total body surface area flame burn injury model. The skin basement macrophages were separated from the skin of normal rats and the wound skin of burned rats and cultured. At 1, 6, and 12 h after intervention, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 protein levels were detected by Western blot, and ERK, p38, and JNK messenger RNA (mRNA) levels were detected by reverse transcription polymerase chain reaction. ResultsDifferences in ERK, p38, and JNK mRNA and protein levels between the normal control group and burned control group were statistically significant (P < 0.05). At the same time point, the ERK, p38, and JNK mRNA and protein levels in the NaSH group were different from those in other groups, and the differences were statistically significant (P < 0.05). ConclusionsHydrogen sulfide has a regulatory effect on ERK, JNK, and p38 in the mitogen-activated protein kinases signaling pathway in macrophages of burned rats.

1,4-bis-3,4,5-trimethoxy-phenyl-tetrahydro-furo(3,4-c) furan from mahogany (swietenia macrophylla king) seed significantly reduces glucose and malondialdehyde levels in diabetic wistar rats

Background: Diabetes mellitus (DM) is an urgent global health issue with increased annual prevalence. The uncontrolled hyperglycemia may induce an oxidative stress state which could lead to the development of diabetic related complications. Several studies showed that mahogany seed contains 1,4-bis-3,4,5-trimethoxy-phenyl-tetrahydro-furo(3,4-c) furan which has glucose-lowering properties. However, its efficacy toward oxidative stress condition is yet to be investigated.Objectives: This study aimed to examine the activity of 1,4-bis-3,4,5-trimethoxy-phenyl-tetrahydro-furo(3,4-c) furan in reducing the malondialdehyde (MDA) level as oxidative stress biomarker and blood glucose levels in diabetic rats.Method: 36 male Wistar rats were used and divided randomly into six groups: Normal control, DM, DM+glibenclamide, DM+isolate10, DM+isolate20, and DM+Isolate40. The isolate and glibenclamide were given for 21 consecutive days. Streptozotocin and nicotinamide were used to induce the diabetic model. Levels of glucose and MDA were measured in successive phases: Before induced by streptozotocin and nicotinamide; before treatment; and after 7, 14, and 21 days of treatment.Results: Within 21 days of treatment, mean glucose and MDA levels in each therapy group: (DM+glibenclamide, DM+isolate10, DM+isolate20, and DM+Isolate40) showed significant decreases over time. Mean of glucose and MDA levels in the therapy groups were significantly lower than in DM (diabetic control) group. Mean of glucose level in DM+Isolate40 group was significantly different from the normal control group but the MDA level showed no significant difference. The results between the DM+Isolate40 group and DM+glibenclamide group showed no significant difference.Conclusion: The 1,4-bis-(3,4,5-trimethoxy-phenyl)-tetrahydro-furo(3,4-c) furan had significant glucose lowering and anti-oxidant effect in diabetic rats.

Neuroprotection of Glibenclamide against Brain Injury after Cardiac Arrest via Modulation of NLRP3 Inflammasome.

Glibenclamide (GBC) improves cerebral outcome after cardiac arrest (CA) in rats. We aim to investigate the effect of GBC on electrophysiological recovery and to explore the mechanism of neuroprotective effects of GBC on the acute stage of brain injury after the return of spontaneous circulation (ROSC) in a rodent model of CA. 16 anesthetized male Wistar rats subjected to 8-min asphyxia-CA were randomly assigned to the GBC or control group (N=8 each group). GBC was administered with a loading dose of 10ug/kg i. p. injection 10 min after ROSC and followed with a maintaining dose of 1.6ug/kg per 8 hours throughout the first 24 hours. Quantitative measures of EEG-information quantity (qEEG-IQ) and neurological deficit score (NDS) were used to predict and evaluate the functional outcome. There was a significant improvement of NDS in rats treated with GBC compared with the control group (p <; 0.01). Compared to the control group, the rats treated with GBC showed qEEG-IQ scores that indicated better recovery (p <; 0.001). Meanwhile, early QEEG-IQ was significantly correlated with 72-hr NDS as early as 45min after ROSC. Furthermore, on the molecular basis, the NLRP3 inflammasome was strongly activated in the hippocampal CA1 area 3 days after CA in control rats, which was suppressed with GBC treatment. Taken together, GBC treatment markedly improved electrophysiological and neurologic outcomes of the acute brain injury after CA. These neuroprotective effects may be associated with the attenuation of inflammatory response via down-regulation of NLRP3 inflammasome signal.

Exploratory analysis of oral glibenclamide in acute ischemic stroke

Intravenous glibenclamide (GBC) exerts neuroprotection in both preclinical and preliminary clinical studies. This study explored the safety and potential efficacy of oral GBC in patients with acute hemispheric infarction. During January 2017 and August 2017, adult volunteers were recruited to receive oral GBC treatment, if they presented with an acute anterior ischemic stroke and a National Institute of Health Stroke Score of ≥8. Controls were those who met the above inclusion criteria and had not been on GBC or other sulfonylureas prior to stroke or after hospitalization. Propensity score matching (PSM) was performed to balance baseline characteristics. The primary endpoint was the score on the modified Rankin Scale (mRS) at 6months. We included 213 patients in the unmatched cohort (20 in the GBC group and 193 in the control group) and 40 patients (20 in each group) in the matched cohort. In both cohorts, GBC treatment did not increase the risks of early death, hypoglycemia, and early neurological deterioration. Although GBC did not substantially improve 6-month functional outcome that measured in shift analysis of mRS, a slight trend toward less severe disability and death (mRS 5-6) was observed. In the matched cohort, GBC treatment was associated with lighter brain edema, when CED score was used for evaluation. In this study, oral GBC is safe in treating acute hemispheric infarction and might have potential in preventing brain edema and consequential severe disability and death. An adequately powered and randomized trial is warranted.

Comparison of the Hyperglycemic Control of M. oleifera Leaves Aqueous Extract and Glibenclamide Tablets in Alloxan Monohydrate Induced Diabetic Rats

Introduction: Diabetes being one of the commonest non-communicable diseases worldwide has no cure. The available hypoglycemic drugs are costly, and have associated long-term side effects. M. oleifera leaves are used in many countries in Africa and Asia to treat diabetes. The study compared the hyperglycemic control of M. oleifera leaves aqueous extract and Glibenclamide tablet in alloxan monohydrate induced diabetic rats.&#x0D; Methods: Twenty-four female Wistar albino rats, made diabetic using alloxan monohydrate, received either M. oleifera extract, glibenclamide or distilled water were delivered intragastric. The mean body weight and mean fasting blood sugar were measured over a period of 28 days. &#x0D; Results: Rats that received distilled water had a mean fasting blood sugar of 329.3+44.9 mg/dl at the beginning, which increased to 448.0+189.9 mg/dl on day 14; all the rats were dead by day 21. The rats that received M. oleifera had blood sugar 443.4+134.7 mg/dl at the beginning, dropped to 166.5+162.79 mg/dl by day 14, and to 88.7+41.0 mg/dl by day 28. Rats that received glibenclamide had blood sugar 517.6+139.3mg/dl at the beginning, dropped to 209.0+201.9 mg/dl on day 14, and to 89.7+42.85 mg/dl on day 28. The blood sugar of the M. oleifera and glibenclamide groups reached normal level by day 21 and remained within the normal range up to day 28. Conclusion: Moringa oleifera leaves aqueous extract has similar pattern to glibenclamide tablet in causing hypoglycemia to alloxan monohydrate induced diabetic rats.

SAT-141 Effect of Vildagliptin versus Glibenclamide on Glycemic Variability and Endothelial Function in Individuals with Type 2 Diabetes and Hypertension: A Randomized Controlled Trial

Introduction: Glycemic variability has been considered as an important factor in the development of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM). High glycemic variability causes endothelial dysfunction and increased oxidative stress. Among the drugs for T2DM, dipeptidyl peptidase-4 (DPP-4) inhibitors improve endothelial function and decrease glycemic variability. Objectives: To investigate the effects of vildagliptin, a DPP-4 inhibitor, compared with glibenclamide on the glycemic variability and endothelial function of patients with T2DM and hypertension (HT). Methods: Prospective, randomized, open, drug-controlled study. Fifty patients older than 35 years with T2DM and HT without CVD were randomized to receive vildagliptin (n=25) or glibenclamide (n=25), in addition to metformin in both groups. Laboratory tests and analysis of endothelial function were performed before and 12 weeks after treatment. Endothelial function, defined by the reactive hyperemia index (RHI), was analyzed by peripheral artery tonometry (endo-PAT2000). The glycemic variability was evaluated by capillary glycemia with intermittent monitoring device, 6 measures/day, for 3 days, before and after 12 weeks of treatment. The calculation of the standard deviation (SD) of the means of glycemia was used to evaluate the glycemic variability. Results: Glycemic variability decreased in the vildagliptin group, defined by median of SD: before 35.2 mg/dL (13.9 - 59.7) vs 30.7 mg/dL (16.1 - 64.3) after treatment (p=0.037) and did not change with glibenclamide, 37.6 (16.0 - 54.9) vs 37.5 mg/dL (16.5 - 80.03) (p=NS). Glycated hemoglobin was similar in both groups at baseline and decreased after 12 weeks, not significantly (8.3% ± 1.0 vs 8.0% ± 1.34, p=0.18 for vildagliptin, 7.9% ± 0.9 vs 7.5% ± 1.4, p=0.17 for glibenclamide). The fasting glycemia decreased in the vildagliptin (166 ± 38.7 mg/dL vs 147.5 ± 42.6 mg/dL, p=0.01) and glibenclamide groups (164 ± 43.5 mg/dL vs. 139 ± 54 mg/dL, p=0.01), with no difference between them. There were no changes in the RHI before and after treatment in both groups (2.34 ± 0.58 vs 2.24 ± 0.60, for vildagliptin, p=NS; 2.36 ± 0.51 vs 2.33 ± 0.49, p=NS for glibenclamide) and there was no difference between groups. There was no correlation between glycemic variability and RHI. Conclusions: Vildagliptin reduces glycemic variability, but has no action on endothelial function, evaluated by endo-PAT2000.

Role of metformin and glibenclamidein controlling gestational diabetes mellitus

Aim of the work: The aim of this study is to compare metformin and glibenclamide in treatment of gestational diabetes mellitus regarding the efficacy in glycemic control and safety.Patients and Methods: Eighty patients aged between 18 and 40 years who were diagnosed to have gestational diabetes mellitus between 16 and 34 weeks that was failed to be controlled by diet and exercise and required medical therapy were recruited. They were allocated to either metformin or glibenclamide therapy. The primary outcome was failure of glycemic control according to fasting and postprandial glucose values. Secondary outcomes were obstetric outcomes, maternal and neonatal complications.Results: Patients in metformin group had significantly higher failure of glycemic control than patients in glibenclamide group (10 cases in metformin group versus 3 cases in glibenclamide group; p=0.003). Also, mean fasting glucose level was significantly higher in metformin group than glibenclamide group (87.38 ± 7.4 and 82.42 ± 6.4 mg/dl, respectively, p= 0.005), while both groups had comparable post-prandial glucose levels (p= 0.11).Both groups had comparable rate of maternal and neonatal complications. There was no significant difference between both groups regarding gestational age and mode of delivery.However, more neonates developed hypoglycemia <40 mg/dl in glibenclamide group than metformin group (11 and 6, respectively, p= 0.025).Conclusion: Metformin and glibenclamide are comparable oral drugs for treatment of gestational diabetes that requires medical treatment regarding maternal and fetal outcomes with preference of glibenclamide in terms of better glycemic control.

Effects of Pistacia atlantica on Oxidative Stress Markers and Antioxidant Enzymes Expression in Diabetic Rats

Introduction: Diabetes mellitus (DM) affects many patients all over the world. It involves different parts of the body, such as brain, eyes, kidneys, vessels, and so on. The lack of balance between free radicals and antioxidants is a possible mechanism involved in the pathogenesis of diabetes. Antioxidant treatment, especially natural forms, can be a beneficial solution. Therefore, we evaluated the effects of Pistacia atlantica oleoresin (PAO) on oxidative stress markers and antioxidant enzymes expression in diabetic rats.Method: Fifty adult male Wistar rats were allotted randomly into five groups as follow: control group, diabetic control group, glibenclamide control group, diabetic glibenclamide group, diabetic treated group with 200 mg/kg PAO. Then PAO was prepared and analyzed by gas chromatography/mass spectroscopy (GC/MS). LD50 was also estimated for essential oil. Oxidative stress markers and antioxidant enzyme including malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were also measured. The expression of GPx, CAT, and SOD genes was investigated using real-time polymerase chain reaction (PCR).Results: The main constituents of essential oil gum were beta-pinene (29.38%), followed by alpha-pinene (18.15%), myrcene (7.36%), trans-pinocarveol (7.15%), and camphene (4.12%). Diabetes induced an increased level of MDA (69.92 ± 3.92 vs. 43.76 ± 3.73) and decreased levels of GSH (2.57 ± 0.40 vs. 7.05 ± 1.59), GPx (11.66 ± 2.2 vs. 16.38 ± 2.1), CAT (12.17 ± 3.38 vs. 18.7 ± 2.66), and SOD (0.78 ± 0.67 vs. 2.41 ± 0.46). In contrast, PAO treatment significantly decreased MDA (54.59 ± 12.54 vs. 69.92 ± 3.92) and increased GSH (4.5 ± 0.89 vs. 2.57 ± 0.40), GPx (25.86 ± 5.37 vs. 11.66 ± 2.2), CAT (22.69 ± 0.36 vs. 12.17 ± 3.38), and SOD (3.65 ± 1.08 vs. 0.78 ± 0.67) (p < 0.05). Moreover, our results indicated that both GPx and CAT mRNA levels significantly increased approximately 4.46 and 6.23 times in rats fed with 200 mg/kg of PAO, more than that of the healthy control group, respectively (p < 0.01 and p < 0.001, respectively). Also, the average expression level of SOD was also significantly 1.57 higher in rats fed with 200 mg/kg of PAO in comparison to the diabetic control group (p < 0.05).Conclusion: The results indicated that PAO could be propose as an agent that protects the body against diseases that are associated with oxidative stress.

Comparative Effects of Metformin and Glibenclamide on Aortic Reactivity to Vasodilator and Vasoconstrictor Agents in STZ-Induced Diabetic Rats

Background: Diabetes is an important risk factor for cardiovascular events. Endothelial dysfunction is the main reason cause of disability and death in diabetic patients and death. The present study investigates the effects of metformin and glibenclamide on vasoconstrictive and vasodilative responses in the diabetic rat aorta. Methods: Rats were divided into four experimental groups (control, STZ-diabetic, metformin and glibenclamide treated diabetic rats). Treated rats received metformin (300 mg/kg) or glibenclamide (5 mg/kg) daily by gavage for 6 weeks. Thoracic aortic rings were mounted in an organ bath system, then contractile and dilatation responses induced by acetylcholine (ACh), phenylephrine (PE), potassium chloride (KCl) and sodium nitroprusside (SNP) were evaluated in different situations. Results: Blood glucose level in glibenclamide group at in days 24 and 45 was were significantly lower than diabetic group. Metformin and glibenclamide significantly reduced the contractile responses to higher concentrations of PE (10-6 - 10-5 M) compared to diabetic group. The mMetformin and glibenclamide significantly reduced the contractile responses to concentrations of KCl (50 and 60 mM) compared to diabetic group. The relaxation responses to Ach 10-8 M, was increased in metformin and glibenclamide groups than compared to the diabetic group. The relaxation responses to Ach 10-7 - 10-5 M were significantly higher in both treated groups compared to diabetic group. Conclusion: The chronic administration of metformin or glibenclamide has a significant hypoglycemic effect and improves aortic reactivity to vasoconstrictor and vasodilator agents in STZ-induced diabetic rats. No significant difference was found regarding thein effects of metformin and glibenclamide on vasoconstrictive and vasodilative responses in aorta.

Effect of vildagliptin versus glibenclamide on endothelial function and arterial stiffness in patients with type 2 diabetes and hypertension: a randomized controlled trial.

Several trials have reported that dipeptidyl peptidase-4 (DPP-4) inhibitors, used to treat type 2 diabetes (T2DM), improve endothelial function. The current study investigated the effects of vildagliptin, a DPP-4 inhibitor, compared to glibenclamide on endothelial function, arterial stiffness, and blood pressure in patients with T2DM and hypertension. Patients aged over 35years with T2DM and hypertension, but without cardiovascular disease, were randomly allocated to treatment with vildagliptin (n = 25) or glibenclamide (n = 25). Both groups took metformin. Endothelial function was evaluated by peripheral artery tonometry (Endo-PAT 2000) to calculate the reactive hyperemia index (RHI) and arterial stiffness. Primary outcome was change in the RHI after 12 weeks of treatment. Twenty-four-hour non-invasive ambulatory blood pressure monitoring was performed using a Mobil-O-Graph® 24-h PWA monitor. Arterial stiffness was assessed using the augmentation index corrected for 75bpm (AIx75), pulse wave velocity (PWV) and central systolic blood pressure (cSBP). There were no changes in the RHI in the vildagliptin group (before 2.35 ± 0.59; after 2.24 ± 0.60; p value = NS) or in the glibenclamide group (before 2.36 ± 0.52; after 2.34 ± 0.50; p value = NS), with no differences between groups (p value = NS). There was also no difference between vildagliptin and glibenclamide treatment in respect to AIx75 (p value = NS), cSBP (p value = NS) or PWV (p value = NS). Vildagliptin and glibenclamide similarly do not change the endothelial function and arterial stiffness after 12 weeks of treatment in diabetic and hypertensive patients without cardiovascular disease. Thus, vildagliptin has a neutral effect on vascular function. ClinicalTrials.gov: NCT02145611, registered on 11 Jun 2013.

Effects of amlodipine and valsartan on glibenclamide-treated streptozotocin-induced diabetic rats

Diabetes mellitus (DM) is a spectrum of metabolic disorders, arising from pathologic mechanisms, resulting in hyperglycaemia. Diabetes and hypertension frequently occur together and are leading risk factors for cardiovascular complications. This study examined the effects of amlodipine and valsartan on glibenclamide-treated streptozotocin-induced diabetic rats.Male albino rats (200–350 g) were fasted overnight and DM was induced by a single dose 40 mg/kg of streptozotocin (i.p.). After 48 h, DM was confirmed (blood sugar ≥200 mg/dl) and the animals were grouped into normal rats with no drug treatment, untreated diabetic animals and groups treated with glibenclamide, glibenclamide plus amlodipine, and glibenclamide plus valsartan. After six weeks treatment, animals were sacrificed under chloroform anaesthesia. Kidney, liver, lung, heart and blood were collected for histology, haematological and biochemical analyses.Untreated diabetic rats had 100% mortality before 6 weeks but addition of valsartan to glibenclamide improved survival rate (71.4% compared with 57.4% in glibenclamide-treated) and blood glucose control but this was not so with glibenclamide plus amlodipine-treated group with 50% survival rate. Treatment ameliorated pathologic changes and there was histologic evidence of organ protection among the various treatment groups when compared with the untreated diabetic group. Addition of valsartan to glibenclamide improved treatment outcome compared to when glibenclamide was used alone but this was not so with the addition of amlodipine to glibenclamide.

Impact of treatment with glibenclamide or vildagliptin on glucose variability after aerobic exercise in type 2 diabetes: A randomized controlled trial

AimsTo evaluate the glucose variability, oxidative stress, metabolic and cardiovascular responses after an aerobic exercise session in diabetic patients on treatment with metformin plus vildagliptin or glibenclamide. MethodsParallel clinical trial including patients with type 2 diabetes treated with metformin plus vildagliptin or glibenclamide for 12 weeks. Glucose variability, oxidative stress, metabolic (plasma glucose, insulin and glucagon-like-peptide-1) and cardiovascular responses were evaluated at rest, during and after a 30 min aerobic exercise session (70% of the peak heart rate). ResultsThirteen patients were included, seven in vildagliptin group (METV) and six in glibenclamide group (METG), baseline glycated hemoglobin (HbA1c) 8.8 ± 0.3%. Treatment reduced HbA1c (1.2% and 1.5% for METV and METG, respectively). The aerobic exercise session did not change glucose variability in both groups. A decrease in glucose during exercise recovery was found, with area under the curve lower in the METG vs. METV (p = 0.04). After the intervention, systolic blood pressure (SBP) decreased in both groups. Patients treated with vildagliptin showed lower SBP variability compared to those treated with glibenclamide. ConclusionsBesides improvement in glucose control and reduction of SBP obtained by both treatments, lower blood pressure variability was observed in patients receiving vildagliptin. Glucose variability remained unaffected by both interventions and the exercise session.