Decline In Blood Glucose Levels Research Articles

Long-term high-fat diet's impact on synaptic plasticity in the visual cortex and hippocampus neurons: an experimental study

Objective: To investigate the effects and mechanisms of long-term high-fat diet on synaptic plasticity in the visual cortex and hippocampus neurons of juvenile mice. Methods: This was an experimental study. Twenty-four 4-week-old male C57BL/6J mice were randomly divided into two groups, using a randomized numerical table, with 12 mice in each group. The ND group was fed a normal diet, while the HFD group was fed a high-fat diet. After 12 weeks of feeding, mouse body weight, body fat percentage, glucose tolerance, and blood lipid levels were recorded. Six mice from each group were randomly selected using a randomized numerical table, and long-term potentiation (LTP) in the lateral geniculate nucleus (LGN)-primary visual cortex binocular zone (V1B area) and hippocampus CA3-CA1 were recorded in vitro. Field excitatory postsynaptic potentials (fEPSPs) were measured, and the normalized fEPSP slope was calculated to evaluate changes in cortical synaptic plasticity. Subsequently, brain tissue was collected for Golgi staining to observe the development of pyramidal neurons in layers Ⅱ-Ⅲ of the primary visual cortex and CA1 region of the hippocampus, and changes in dendritic spine morphology and quantity were compared. The remaining six mice from each group were euthanized, and brain tissue was collected for transmission electron microscopy to observe ultrastructural changes in the visual cortex V1B area and hippocampus CA1 region neurons. Independent samples t-test was used for statistical analysis. Results: After 12 weeks of feeding, the body weight of mice in the HFD group was (29.17±1.63) g, significantly lower than the ND group which was (37.99±6.87) g (t=4.33, P<0.001). The body fat percentage in the HFD group was 1.09%±0.22%, which was higher than the ND group with 0.85%±0.09% (t=2.50, P=0.032). HFD mice showed a significant increase in blood glucose level 30 minutes after glucose injection, reaching (17.80±3.94) mmol/L, compared to the ND group with (23.10±1.48) mmol/L (t=3.07, P=0.013). At 60 minutes after glucose injection, the difference in blood glucose levels between the ND group [(13.58±2.39) mmol/L] and the HFD group [(23.70±3.56) mmol/L] was statistically significant (t=5.40, P<0.001). Subsequently, both groups showed a decline in blood glucose levels, and at 120 minutes after glucose injection, the blood glucose level in the ND group decreased to (8.50±1.05) mmol/L, while the HFD group remained at a higher level of (16.03±4.17) mmol/L, showing a statistically significant difference (t=3.91, P=0.004). The serum total cholesterol levels in the ND and HFD groups were (4.08±0.35) mmol/L and (10.80±0.90) mmol/L, respectively, with the HFD group higher than the ND group (t=15.23, P<0.001). However, there was no significant difference in triglyceride levels (P>0.05). The high-density lipoprotein cholesterol level in the ND group was (2.12±0.57) mmol/L, while in the HFD group, it was (1.28±0.15) mmol/L, with the HFD group lower than the ND group (t=3.15, P=0.014). Non-high-density lipoprotein cholesterol level in the HFD group was (11.06±1.46) mmol/L, significantly higher than the ND group with (2.28±0.43) mmol/L (t=12.88, P<0.001). In the hippocampal CA3-CA1 pathway, the fEPSP slope increased by 239.1%±88.8% of baseline in the ND group, while in the HFD group, it was only 147.6%±31.6% of baseline, indicating lower LTP compared to the ND group (t=7.20, P<0.001). For the LGN-V1 pathway, the fEPSP slope increased by 204.8%±67.0% of baseline in the ND group, while in the HFD group, it was 121.1%±15.7% of baseline, showing reduced LTP compared to the ND group (t=9.11, P<0.001). Regarding the visual cortex, in the V1B area of the ND group, the number of dendritic spines per 10 μm was (1.31±1.14), while in the HFD group, it was (0.77±0.43), demonstrating a significant decrease in dendritic spine density (t=3.45, P<0.001). The proportion of mature dendritic spines in the ND group was 69.98%, while non-mature dendritic spines accounted for 30.02%. In contrast, the HFD group had 45.76% mature dendritic spines and 54.24% non-mature dendritic spines. Regarding changes in hippocampal CA1 pyramidal neurons, the cell bodies and axons were not damaged, but HFD group neurons exhibited simplified dendritic structures with reduced branching. The number of dendritic spines per 10 μm was (10.25±3.84) in the HFD group and (25.22±8.21) in the ND group, indicating significantly lower dendritic spine density in the HFD group (t=12.42, P<0.001). The proportion of mature dendritic spines in the ND group was 70.88%, while non-mature dendritic spines accounted for 29.12%. In contrast, the HFD group had 47.37% mature dendritic spines and 52.63% non-mature dendritic spines. Moreover, the ultrastructure of neurons in the visual cortex V1B area and hippocampus CA1 region of HFD mice showed evident damage, with disrupted cell structures, swollen and vacuolated mitochondria, reduced or even disappeared mitochondrial cristae, and decreased synaptic quantity with damaged structure. Conclusions: Long-term high-fat diet in juvenile mice leads to abnormal development and functional maturation of synapses in the visual cortex and hippocampal regions. Dendrites, as the foundation of synaptic structures, undergo abnormal development, which can cause alterations in synaptic plasticity of related neural circuits.

In-depth in-vitro and in-vivo anti-diabetic evaluations of Fagonia cretica mediated biosynthesized selenium nanoparticles

Therapeutic moieties derived from medicinal plants as well as plants-based ecofriendly processes for producing selenium nanoparticles have shown great promise in the management of type 2 diabetes mellitus (T2DM). The current study was aimed to assess the anti-diabetic potentials of Fagonia cretica mediated biogenic selenium nanoparticles (FcSeNPs) using in-vitro and in-vivo approaches. The bio-synthesized FcSeNPs were characterized using various techniques including UV–VIS spectrophotometry and FTIR analysis. The in-vitro efficacy of FcSeNPs were assessed against α-glucosidase, α-amylase enzymes as well as the anti-radical studies were performed using DPPH and ABTS free radicals scavenging assays. For in-vivo studies, 20 Male Balb/C albino-mice were randomly divided into 4 groups (n = 5) including normal group, disease group (Diabetic group with no treatment), control group and treatment group (Diabetic group treated with FcSeNPs). Further, biochemistry markers including pancreas, liver, kidney and lipid profile were assessed for all treatment groups. The FcSeNPs exhibited a dose-dependent inhibition against α-amylase and α-glucosidase at 62–1000 µg mL−1 concentration with IC50 values of 92 and 100 µg mL−1 respectively. In antioxidant experiments, the FcSeNPs demonstrated significant radicals scavenging effect against DPPH and ABTS radicals. In STZ-induced diabetic mice, a considerable decline in blood glucose level was observed after treatment with FcSeNPs. Anti-hyperglycemic effect of FcSeNPs treated animals were high (105 ± 3.22**) as compared to standard drug (128.6 ± 2.73** mg dL−1). Biochemical investigations revealed that all biochemical parameters for pancreas, liver function, renal function panel and lipid profile were significantly lowered in FcSeNPs treated animals. Our findings indicate a preliminary multi-target efficacy for FcSeNPs against type-2 diabetes and thus warrant further detailed studies.

Therapeutic Potential of Clove Essential Oil in Diabetes: Modulation of Pro-Inflammatory Mediators, Oxidative Stress and Metabolic Enzyme Activities.

Type 1 diabetes is characterized by insulin deficiency due to the destruction of pancreatic β cells, leading to hyperglycemia, which in turn induces vascular complications. In the current study, we investigated the effect of intraperitoneal administration of clove essential oil (CEO: 20 mg/kg body weight) on certain oxidative stress and glucose metabolism enzymes, as well as the expression of proinflammatory mediators. Administration of CEO to diabetic rats showed a significant decline in blood glucose levels, total cholesterol, and xanthine oxidase, compared to the streptozotocin group. Furthermore, these treated rats elicited a notable attenuation in the levels of lipid peroxides, and thiols groups in both liver and brain tissues. The activities of antioxidant and metabolic enzymes were reverted to normality in diabetic upon CEO administration. In addition to its protective effects on red blood cell hemolysis, CEO is a potent α-amylase inhibitor with an IC50 =298.0±2.75 μg/mL. Also, treatment of diabetic rats with CEO significantly reduced the iNOS expression in the spleen. Our data showed that CEO has potential beneficial effects on diabetes, which can possibly prevent the pathogenesis of diabetic micro- and macrovascular complications.

Combined antidiabetic potential of camel milk yogurt with Cinnamomum verum and Stevia rebaudiana by using rodent modelling.

This study aimed to evaluate anti-diabetic potential of functional camel milk yogurt enriched with Cinnamomum verum and Stevia rebaudiana that not only mask its peculiar flavour rather have an antidiabetic effect as well. Sixty-three pathogen free STZ-induced albino Wistar rats were categorized into 7 groups on the basis of treatments. From each treatment group three animals were dissected periodically at 0, 7 and 21days of study to determine the effect of all treatments on physicochemical parameters, serum glucose, serum chemistry and haematology. The study revealed that the mean blood glucose level in the untreated control group was within normal range (100-108mg/dl) while there was noticeable decrease in mean blood glucose level of all the treated groups during three weeks' trial. Decline in blood glucose level (46%) was higher in animal group containing functional camel milk yogurt (T4) at 3rd week of trial as compared to other treatments.

Anti-diabetic Effect of Ethanolic Extracts of Cissus Quadrangularis linn Fruits and Michelia Champaea Leaves in Alloxan Induced Hyperglycaemic Rats and in 3T3L1 Cell Lines

Background: Diabetes is a metabolic disorder that results in increased blood sugar. This study came up with a search for alternative medicines with no or fewer side effects for antidiabetic therapy. Materials and methods: The plants are extracted and screened for phytochemical study of crude extracts. Anti-diabetic activity in alloxan induced hyperglycaemic rats, in single dose study, multiple dose treatment was investigated. In vitro cellular assay using 3T3L1 cell line was performed to check the cell viability with increasing plant extract treatment. Results: Phytochemical investigation reveals the presence of alkaloids, flavonoids, saponins, tannins, steroids, triterpinoids, carbohydrates, and glycosides in both plant extractions. In acute toxicity studies, no mortality was observed with either of the extracts even at a dosage of the level of 5000 mg per kg of body weight. The ethanolic extracts showed a noteworthy decline in blood glucose level in alloxan induced rats in both single and multiple dosage methods. Significant changes were observed in the serum glucose and body weight from day 0 to day 14. The cell viability of the extracts was also comparable with the standard. Conclusion: Our results report that CQ fruits and MC leaves have potent antidiabetic action and on further studies, can be a credible resource in antidiabetic therapy.

Therapeutic Effect of Asphodelus Tenuifolius Against Streptozotocin Induced Diabetic Rats

Background: Diabetes mellitus is a long-lasting metabolic disorder that hinders the capability of the body to utilize food properly and is affected day by day through our diet, exercise, infection and stress. Presently, the trend is more towards natural plant-based products containing potential bio-active components than towards conventional medicines. For the purpose, out of numerous herbs used in common medicines, the subfamily of Asphodelus tenuifolius, used for several ailments, anti-inflmmation, anti-hypertension and antidiuretics etc. Objective: The objective of the present study was to evaluate the therapeutic effect of Asphodelus tenuifolius against streptozotocin induced diabetic rats. Method: The current study was based on the in vitro and in vivo properties of Asphodelus tenuifolius. The in vivo study was conducted that includes the TPC, TFC &amp; DPPH. The in vitro study was also administered that includes the body weight and glucose levels of the rats. The thirty rats were divided into six groups; normal control, disease control, drug control, extracts treatment at 250, 500 and 750 mg/kg respectively. Results: The results depicted that the maximum decline in blood glucose levels of the streptozotocin induced diabetic rats were observed in T5. However, the body weights of the diabetic rats were maintained. Conclusion: Conclusively, Asphodelus tenuifolius plants contain a bio-active component that help to reduce hyperglycemia, maintains body weights in streptozotocin induced diabetic rats.

Effects of Simulated High Altitude on Blood Glucose Levels During Exercise in Individuals With Type 1 Diabetes.

Current exercise guidelines for individuals with type 1 diabetes (T1D) do not consider the impact that high altitude may have on blood glucose levels (BGL) during exercise. To investigate the effect of acute hypoxia (simulated high altitude) on BGL and carbohydrate oxidation rates during moderate intensity exercise in individuals with T1D. Using a counterbalanced, repeated measures study design, 7 individuals with T1D completed 2 exercise sessions; normoxia and hypoxia (~4200 m simulated altitude). Participants cycled for 60 min on an ergometer at 45% of their sea-level V̇O2peak, and then recovered for 60 min. Before, during, and after exercise, blood samples were taken to measure glucose, lactate, and insulin levels. Respiratory gases were collected to measure carbohydrate oxidation rates. Early during exercise (<30 min), there was no fall in BGL in either condition. After 1 h of exercise and during recovery, BGL were significantly lower under the hypoxic condition compared to both pre-exercise levels (P = 0.008) and the normoxic condition (P = 0.027). Exercise in both conditions resulted in a significant rise in carbohydrate oxidation rates, which returned to baseline levels postexercise. Before, during, and after exercise, carbohydrate oxidation rates were higher under the hypoxic compared with the normoxic condition (P < 0.001). The greater decline in BGL during and after exercise performed under acute hypoxia suggests that exercise during acute exposure to high altitude may increase the risk of hypoglycemia in individuals with T1D. Future guidelines may have to consider the impact altitude has on exercise-mediated hypoglycemia.

Nano-formulation of 4-Hydroxy-3-methoxybenzohydrazide: Preparation, characterization and studies of antihyperglycemic and antioxidant activities as evaluated through amelioration of pancreatic Dysfunction in experimental animals

In the present work, nanoparticles of previously synthesized 3a derivatives of vanillic acid were synthesized by the nanoprecipitation method. Nanoparticles were further characterized by UV–vis spectroscopy, FTIR spectroscopy, SEM analysis, XRD and zeta sizer. Diabetes was instigated in Wistar albino rats by intraperitoneal (I.P.) administration of Streptozotocin (60 ​mg/kg body weight). Vanillic acid (100 ​mg/kg), 3a (100 ​mg/kg) and 3aNPs (50 ​mg/kg) body weight were given orally for a period of 21 days. Blood glucose level and biochemical parameters such as cholesterol, triglycerides, LDL, HDL, VLDL and antioxidant parameters were assessed by using diagnostic kits. SEM analysis and PDI of 3aNPs was found to be 0.2 which indicate monodisperse distribution. Significant decline in blood glucose level (p ​< ​0.001) was observed in antidiabetic studies along with the lipid lowering and antioxidant effect in dose-dependent manner. The noted results of the study showed that nanoparticles were found to be effective in treating diabetes.

In silico identification of antidiabetic target for phytochemicals of A. marmelos and mechanistic insights by molecular dynamics simulations

The leaves and fruits of Aegle marmelos (L.) have antidiabetic activity. However, the mode of action and molecules having antidiabetic activity are not known. Hence, we conducted molecular docking of phytochemicals with various molecular antidiabetic targets to find the same. Docking prioritized Dipeptidyl peptidase-4 (DPP-4) as the main target for phytochemicals of Aegle marmelos. DPP-4 inactivates intestinal peptides, glucagon-like peptide-1 (GLP-1), and Gastric inhibitory polypeptide (GIP). GLP-1 and GIP stimulate a decline in blood glucose levels, but DPP-4 inhibits their functions resulting high level of glucose. Hence inhibiting the activity of DPP-4 is a well-known strategy to treat Type 2 diabetes. Therefore, to find a mechanism that may be involved to act as a natural inhibitor of DPP-4, we screened five phytochemicals out of seventy-three based on Virtual Screening, ADMET Drug-likeness analysis, and PAINS filtering. Further, all five phytochemicals, i.e. Aegeline, Citral, Marmesinin, Auraptene, β-Bisabolene, and reference compound subjected MDS for analyzing the stability of docked complexes to assess the fluctuation and conformational changes during protein-ligand interaction. The values of RMSD, RG, RMSF, SASA, and Gibbs energy revealed the good stability of these phytochemicals in the active site pocket of DPP-4 in comparison to reference. Additionally, we have done the pharmacophore analysis, which revealed many common pharmacophore features between screened phytochemicals of A. marmelos and reference molecule. Our results show that these phytochemicals are potential antidiabetic candidates and can be further modified and evaluated to develop more effective antidiabetic drugs against DPP-4 to treat Type 2 Diabetes. Communicated by Ramaswamy H. Sarma

Antidiabetic Activity Test of Sambiloto Capsules (Andrographis paniculata) with Glibenclamide on White Male Mice DDY Strain

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia and metabolic abnormality of carbohydrates, fats, and proteins caused by decreased insulin sensitivity. Glibenclamid as a synthesis drug or traditional medicine such as Sambiloto Capsule could use for diabetes mellitus. Hereditary, people have been using decoction of Sambiloto’s leaves to prevent cold, influenza, fevers, jaundice. The bitterness of Sambiloto (Andrographis paniculata) was also believed to cure diabetes. The purpose of this research was to compare between Sambiloto capsule with Glibenclamid on white male mices DDY strain. The research method was an experimental study using pre and post test control group design, using 15 white male mices DDY strain which were given a glucose load and divided into 3 groups. Negatif control group (CMC Na), positive control group (Glibenclamid), and test group (Sambiloto Capsules). The results blood glucose level of this research was analyzed using Paired T-test and with the 95 % convidence level. The comparison test of antidiabetes activity between Sambiloto Capsule and Glibenklamid on white male mice DDY strain showed that the Sambiloto Capsule had antidiabetic activity viewed from the average decline in blood glucose levels. The degradation of blood glucose levels in Glibenklamid group was faster than Sambiloto Capsule group indicated by the statistical analysis using Paired T-test with the significance level smaller than 0,05 and showed by T-value was great than T-tabel. Conclusion of the research showed that the activity Sambiloto Capsules anti diabetic.

Effect of Ethanol Extract of Tetrapleura tetraptera (Schum and Thonn) Taub Leaves on Oral Glucose Tolerance in Normal, Glucose‐induced and Normotensive Female Wistar Rats

Traditional Medicine is reported the oldest, widely practiced healthcare system in Africa. This practice has further gained momentum in recent years due to its accessibility, affordability and extensive scientific validation. Leaves of Tetrapleura tetraptera are being used in treatment of diabetes, oxidative stress, hyperlipidemia and managing dysfunctional lipid metabolism (a side effect of the use of sulphonylureas as antidiabetics). However, there has been paucity of information on therapeutic synergy. The present study aimed to evaluate the hypoglycemic effect of Tetrapleura tetraptera ethanol leaf extract on blood glucose levels (BGL) in glucose‐induced hyperglycemic and normotensive rats. Mature female Wistar rats with average weight of 120 g were fasted for 12 h then placed into six groups of five rats each. The following treatment schedules were applied accordingly: no treatment (vehicle); glucose (2 g/kg, control); three groups of glucose‐induced hyperglycemia treated with 100 (TT100GLU), 200 (TT200GLU) and 400 (TT400GLU) mg/kg ethanol extract doses of Tetrapleura tetraptera leaves (EtTT) respectively; and 400 mg/kg extract dose of EtTT (TT400, normotensive). Blood glucose concentration through femoral vein was evaluated at 0, 30, 60, 90, 120 and 150 minutes after oral treatment in all cases. Average fasting blood glucose level in all groups at 0 min was 90± 3.71 mg/dL. All treatment groups showed an elevation in BGL at 30 min with values ranging from 86.20 ± 2.22 in vehicle to 107.4 mg/dL in TT400GLU before a progressive decrease in BGL with increase in time. The decline in BGL of treatment groups was generally not significantly different at p&lt;0.05 from control, however, the extract significantly (p&lt; 0.05) reduced blood glucose in normotensive group (TT400GLU) such that at 150 min, BGL dropped to 59.8 mg/dL and animals were showing symptoms of hypoglycemia. Ethanol extract of T. tetraptera leaves possesses the capacity to lower blood glucose levels thus reducing the tendency for hyperglycemic complications. These results further validate its traditional use and it can be proposed that the leaf extract dose should not be administered singly in fasting conditions as it could lead to hypoglycemia.Support or Funding InformationI am a member of American Society for Pharmacology and Experimental Therapeutics (ASPET) with membership ID 0057705Comparison of fasting blood glucose level of various groups. Data are expressed mean ± SEM for 6 groups of 5 rats each with significant difference tested at p&lt;0.05Figure 1

Quality by Design Approach for Developing Lipid-Based Nanoformulations of Gliclazide to Improve Oral Bioavailability and Anti-Diabetic Activity.

The aim of the current investigation was to generate a self-nanoemulsifying drug delivery system (SNEDDS) of gliclazide (GCZ) to address the poor solubility and bioavailability. Ternary phase diagram was created with Capmul MCM C8 NF (oil), Cremophor RH 40 (surfactant), and Transcutol HP (co-surfactant) to distinguish the self-emulsifying region. A D-optimal design was employed with three variables, such as oil, surfactant, and co-surfactant, for further optimization of liquid (L)-SNEDDS. GCZ-loaded L-SNEDDs were analyzed for globule size, polydispersity index (PDI), and solubility. In vitro dissolution of optimized L-SNEDDS exhibited (F5) faster drug release (97.84%) within 30min as compared to plain drug (15.99%). The optimized L-SNEDDS was converted to solid (S)-SNEDDS as a self-nanoemulsifying powder (SNEP) and pellets by extrusion-spheronization. Optimized S-SNEDDS were characterized using Fourier-transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). In vitro dissolution of SNEP (S3) and pellet were 90.54 and 73.76%, respectively, at 30min. In vivo studies showed a twofold rise in bioavailability through SNEDDS with a significant decline in blood glucose levels compared to plain drug suspension suggesting a lipid-based system as an alternative approach for treating diabetes.

Two antidiabetic constituents from Roylea cinerea (D.Don) Baill.

Two antidiabetic compounds named 4-methoxybenzo[b]azet-2(1H)-one (1) and 3β-hydroxy-35-(cyclohexyl-5′-propan-7′-one)-33-ethyl-34-methyl-bacteriohop-16-ene (2) together with stigmasterol and β-sitosterol were isolated from the aerial part of Roylea cinerea (D.Don) Baill. The structures of these compounds were elucidated by advanced spectroscopic methods, including two-dimensional NMR and MS techniques. These compounds were evaluated for their antidiabetic efficacy using in vitro and in vivo methods. Both compounds (1 and 2) showed a significant decline in blood glucose level of alloxan-induced diabetic rats at 10 mg/kg, p.o. when compared with glibenclamide at a similar dose. The in vitro studies revealed that compound 1 reduced α-amylase and α-glucosidase by 83.0 and 78.5%, respectively, whereas compound 2 reduced the same by 58.2 and 58.4%, respectively, at 100 μM. The present study supports the role of R. cinerea in Ayurvedic medicine for diabetes.

Effect of the Aquatic Extract of Stevia on the Serum Level of Interleukin-6 in Streptozotocin-Nicotinamide Induced Diabetic Rats

Background: Diabetes, as a common chronic disorder, is the seventh leading cause of death in the world. This disorder is classified into two major types: type I and type II diabetes mellitus. Recently, researchers have identified a higher level of inflammatory cytokines in patients with type II diabetes, compared to the normal population. Today, plant-based therapies, given their anti-diabetic properties, have attracted the researchers’ attention. One of the medicinal plants with anti-diabetic effects is Stevia rebaudiana Bertoni. Various hypotheses have been proposed to explain how stevioside, as a derivative of Stevia rebaudiana, can cause such a significant decline in blood glucose level. To the best of our knowledge, the exact anti-inflammatory and immunomodulatory effects of the aquatic extract of stevia are not fully understood. Therefore, the current research aimed to evaluate whether stevia can improve the interleukin-6 (IL-6) level in streptozotocin-nicotinamide-induced diabetic rats. Methods: In the present study, a cohort of rats was divided into five groups, each containing 11 rats: (1) normoglycemic group, receiving 1 mL of water; (2) diabetic control group, receiving 1 mL of water; (3) and (4) diabetic groups treated with the aquatic extracts of stevia (400 mg/kg) and metformin (500 mg/kg), respectively; and (5) healthy group treated with the aquatic extract of stevia (400 mg/kg). At the end of the experiment, the rats were sacrificed and blood samples were collected from the heart for evaluating serum IL-6 changes. Statistical analysis was performed, using one-way analysis of variance (ANOVA), followed by the least significant difference (LSD) post-hoc multiple comparison test. Results: The present results showed that IL-6 (P = 0.001) and fasting blood sugar (FBS) (P < 0.001) levels significantly increased in all diabetic groups, compared to healthy rats. Surprisingly, treatment with stevia could significantly reduce FBS (P < 0.001), as well as IL-6 level (P = 0.001) in comparison with the diabetic group. Conclusions: Based on the findings, inflammation can be ameliorated with the whole aquatic extract of stevia, as an anti-diabetic compound. Therefore, by considering IL-6 level as an indicator of insulin resistance, stevia can lead to a decline in IL-6 level and thereby reduce insulin resistance in diabetic patients.

Comparison of efficacy and safety of metformin and vildagliptin versus metformin and glimepiride in patients of Type 2 diabetes mellitus

Background: Diabetes mellitus is a heterogeneous chronic metabolic disorder principally characterized by persistent hyperglycemia resulting from defects in insulin action and/or insulin secretion. In course of time, prolonged hyperglycemia and associated metabolic aberrations result in tissue toxicity manifested as accelerated atherosclerosis, renoretinal microangiopathy, and neuropathy leading to a variety of vascular, neurological, and focal complications. Aim and Objective: The aim of this study is to evaluate the efficacy and safety of metformin and vildagliptin versus metformin and glimepiride in patients with Type 2 diabetes mellitus. Materials and Methods: This is a longitudinal interventional study. A total of 60 patients were enrolled in the study. Those patients who were already on metformin 500 mg bid with poor glycemic control were included in the study. These 60 patients were divided into two groups each consisting of 30 patients. Group A patients received glimepiride 1 mg bid and metformin 500 mg bid. Group B patients received vildagliptin 50 mg bid and metformin 500 mg bid. The total period of the study was 3 months. Results: After 3 months of treatment, both the groups caused a significant decline in blood glucose levels both fasting blood sugar (FBS) as well as postprandial blood sugar (PPBS) levels. There was a significant difference between the two groups in reducing the FBS levels and PPBS. Hemoglobin A1c (HbA1c) was also reduced significantly in both groups at 12 weeks. After 3 months of therapy, there was a reduction in HbA1C in B group. The reduction of HbA1C was not statistically significant between the two groups. Adverse effects were more with metformin and glimepiride group at the end of 3 months therapy. There was a significant difference in the incidence of adverse effects between both the groups. Conclusions: Vildagliptin and metformin combination provided better efficacy comparable to that of glimepiride and metformin combination and resulted in better adverse effect profile with lower risks of hypoglycemia and weight gain.

Finding a Potential Dipeptidyl Peptidase-4 (DPP-4) Inhibitor for Type-2 Diabetes Treatment Based on Molecular Docking, Pharmacophore Generation, and Molecular Dynamics Simulation.

Dipeptidyl peptidase-4 (DPP-4) is the vital enzyme that is responsible for inactivating intestinal peptides glucagon like peptide-1 (GLP-1) and Gastric inhibitory polypeptide (GIP), which stimulates a decline in blood glucose levels. The aim of this study was to explore the inhibition activity of small molecule inhibitors to DPP-4 following a computational strategy based on docking studies and molecular dynamics simulations. The thorough docking protocol we applied allowed us to derive good correlation parameters between the predicted binding affinities (pKi) of the DPP-4 inhibitors and the experimental activity values (pIC50). Based on molecular docking receptor-ligand interactions, pharmacophore generation was carried out in order to identify the binding modes of structurally diverse compounds in the receptor active site. Consideration of the permanence and flexibility of DPP-4 inhibitor complexes by means of molecular dynamics (MD) simulation specified that the inhibitors maintained the binding mode observed in the docking study. The present study helps generate new information for further structural optimization and can influence the development of new DPP-4 inhibitors discoveries in the treatment of type-2 diabetes.

Comparative evaluation of efficacy and safety of combination of metformin-vidagliptin versus metfromin-glimepiride in most frequently used doses in patients of type 2 diabetes mellitus with inadequately controlled metformin monotherapy-A randomised open label study.

Aim and Objective:The aim was to evaluate and compare the efficacy and safety of combinations of metformin-vidagliptin (MF-VG) and metfromin-glimepiride (MF-GP) in type 2 diabetes mellitus (T2DM) patients.Materials and Methods:A comparative randomized open-label trial was conducted on patients with uncomplicated T2DM, on treatment with MF for 4 months out of which on maximum tolerated dose of MF (1000-2500 mg/day) for 4 weeks, glycosylated Haemoglobin [HbA1c]) ≥6.5%, fasting blood glucose (FBG) ≥126 mg/dl and post prandial glucose (PPG) ≥200 mg/dl were included in the study. Patients were randomized to receive MF (500 mg BD) + VG (50 mg BD) or MF (500 mg BD) + GP (2 mg BD).Results:Both the groups caused significant decline in blood glucose levels both FBG as well as PPG levels (P < 0.01). HbA1c was also reduced significantly in both groups at 12 weeks (P < 0.01). Total serum cholesterol, triglycerides, low-density lipoprotein and very low-density lipoprotein decreased significantly, whereas high-density lipoprotein levels increased significantly from baseline levels in both the groups (P < 0.01). Intergroup comparison failed to demonstrate any statistical difference on all of above parameters. Both weight and body mass index did not alter statistically from baseline in either of the groups as well as demonstrated no difference statistically on comparison (P > 0.05). At the end of the study, both liver functions tests and renal functions tests remained unaltered statistically and within normal clinical range in both the groups (P > 0.05). However, hypoglycemia and other adverse events were numerically more in MF + GP group.Conclusion:Both the regimens on comparison revealed similar efficacy and safety thereby failing to prove superiority over each other.

HD047703, a New Promising Anti-Diabetic Drug Candidate: In Vivo Preclinical Studies.

G-protein coupled receptor 119 (GPR119) has emerged as a novel target for the treatment of type 2 diabetes mellitus. GPR119 is involved in glucose-stimulated insulin secretion (GSIS) from the pancreatic β-cells and intestinal cells. In this study, we identified a novel small-molecule GPR119 agonist, HD047703, which raises intracellular cAMP concentrations in pancreatic β-cells and can be expected to potentiate glucose-stimulated insulin secretion from human GPR119 receptor stably expressing cells (CHO cells). We evaluated the acute efficacy of HD047703 by the oral glucose tolerance test (OGTT) in normal C57BL/6J mice. Then, chronic administrations of HD047703 were performed to determine its efficacy in various diabetic rodent models. Single administration of HD047703 caused improved glycemic control during OGTT in a dose-dependent manner in normal mice, and the plasma GLP-1 level was also increased. With respect to chronic efficacy, we observed a decline in blood glucose levels in db/db, ob/ob and DIO mice. These results suggest that HD047703 may be a potentially promising anti-diabetic agent.

Is there cross talk between portal and hypothalamic glucose-sensing circuits?

The detection of hypoglycemia stems from sensors located in both the periphery and within the central nervous system and likely involves a complex circuit that incorporates information from both peripheral and central components. Glucose sensors located in each of these regions play a unique role in hypoglycemia detection that appears to be at least in part dependent on the rate of fall of blood glucose levels. Sensors that are located within the brain, particularly those located within the ventromedial hypothalamus (VMH), appear to dominate when glucose levels fall rapidly (1–3). While still speculative, it has been proposed that this may serve as a protective fail-safe mechanism that is put in place to prevent a sudden and potentially catastrophic depletion of fuel supply to the brain. On the other hand, glucose sensors located in the portal-mesenteric vein (PMV) have been proposed to be more important for detecting a gradual decline in blood glucose levels (4–6). Interestingly, it has recently been suggested that central and peripheral sensors appear to operate independently from one another as lesions that are made to PMV sensors do not influence the ability of central sensors to detect rapid-onset hypoglycemia but did prevent the detection of slow-onset hypoglycemia (7). This implies that these two sets of hypoglycemia sensors may exert differential roles in glucose sensation and glucose counterregulation and that they are not merely redundant mechanisms. Hypoglycemic signals from PMV glucose sensors that are transmitted to the central nervous system appear to use central pathways that are independent from those used by hypothalamic centers. Although much of our current understanding of glucose-sensing mechanisms stems from work that was conducted in the VMH of the brain (8), the existence of a relay circuit between PMV sensors, the brain, and the sympathoadrenal system has been postulated …

Modulatory effects of diosgenin on attenuating the key enzymes activities of carbohydrate metabolism and glycogen content in streptozotocin-induced diabetic rats.

Fenugreek and its active compound diosgenin are ancient herbal medicines recommended by the World Health Organization. In this study, the effect of diosgenin on changes in carbohydrate metabolic enzymes and glycogen content in muscle and kidneys of streptozotocin-induced diabetes rats were evaluated. Diabetes was induced in male albino Wistar rats by intraperitoneal administration of streptozotocin. The diosgenin at different doses (15, 30 and 60 mg/kg body weight) was administered orally to normal and streptozotocin-diabetic rats for 45 days. Streptozotocin intoxication led to a significant increase (p<0.05) in blood glucose and a decrease in insulin levels. The carbohydrate metabolic enzymes and glycogen content were also altered. The daily oral administration of diosgenin at different doses (15, 30 and 60 mg/kg body weight) to diabetic rats for 45 days resulted a significant (p<0.05) decline in blood glucose level and a significant increase in plasma insulin level. The altered activities of carbohydrate metabolic key enzymes in muscle and kidneys of diabetic rats were significantly (p<0.05) reverted to near normal level by the administration of diosgenin. The obtained results were compared with glibenclamide, a standard oral hypoglycemia drug. The modulatory effects of diosgenin on attenuating the activities of carbohydrate metabolic enzymes afford a promise for persistent use for the treatment of diabetes in the future, even though clinical studies to evaluate this possibility may be warranted.