Reduced Serum Glucose Research Articles

PFOS induced lipid metabolism disturbances in BALB/c mice through inhibition of low density lipoproteins excretion

Male BALB/c mice fed with either a regular or high fat diet were exposed to 0, 5 or 20 mg/kg perfluorooctane sulfonate (PFOS) for 14 days. Increased body weight, serum glucose, cholesterol and lipoprotein levels were observed in mice given a high fat diet. However, all PFOS-treated mice got reduced levels of serum lipid and lipoprotein. Decreasing liver glycogen content was also observed, accompanied by reduced serum glucose levels. Histological and ultrastructural examination detected more lipid droplets accumulated in hepatocytes after PFOS exposure. Moreover, transcripitonal activity of lipid metabolism related genes suggests that PFOS toxicity is probably unrelevant to PPARα's transcription. The present study demonstrates a lipid disturbance caused by PFOS and thus point to its role in inhibiting the secretion and normal function of low density lipoproteins.

Menaquinone benefits weight control and improves inflammatory biomarkers in high‐fat diet‐induced obese rats (815.1)

Vitamin K is a co‐factor for γ‐glutamic carboxylase, which is an essential enzyme for the γ‐carboxylation of vitamin K‐dependent proteins. Menaquinone (vitamin K2) has been reported to have favorable effects on bone metabolism and energy metabolism. In the present study we investigated the effects of the long‐term supplementation effects of menaquinone on inflammatory status and weight control in high‐fat diet (HFD)‐induced obese mice. A total of twenty‐one male, 4‐week‐old C57BL/6 mice were fed and randomly divided into 3 groups (7 animals in each group; randomized block design), a normal diet (ND), 45% HFD and a 45% HFD + menaquinone (HFD ‐K2) for 3 months. Weight change, adipose tissue weight and serum proinflammatory cytokines were determines.Compared with the ND, the HFD increased total fat mass, leptin, osteoprotogerine, and fasting blood glucose levels. Consumption of HFD containing menaquinone resulted in significantly less weight gain (12% less, p<0.05). Interestingly, menaquinone supplementation significantly decreased the total fat accumulation (p<0.05) and leptin levels (p<0.05) and reduced serum glucose by 17% compared with the HFD group.In conclusion, the present study demonstrates that menaquinone supplementation had favorable effects on weight control and body composition possibly through suppressing inflammation.Further studies on the mechanism of menaquinone supplementation in the regulation of body fat accumulation would provide valuable data on the prevention of lifestyle related disorders, including diabetes and obesity.Grant Funding Source: Funded by the Ministry of Education, Science and Technology in Korea(project no:2012R1A1A3012499

Influence of chromium propionate on the carcass characteristics and immune response of commercial broiler birds under normal rearing conditions

The study investigated the effect of supplementation of chromium propionate at different dosage levels (100 to 3,200 µg/kg of elemental chromium in feed) on the performance, carcass characteristics, and immune response of broiler birds. The study was conducted on male broiler chickens (Cobb 400) for a period of 42 d as per the completely randomized design. Seven hundred 1-d-old birds were randomly segregated into 7 treatment groups, each with 10 replicates, and each replicate having 10 birds. Weight gain, feed intake, carcass characteristics, immune response, and the serum biochemical parameters of birds were studied during the supplementation period. There was no significant response to chromium supplementation on weight gain, feed intake, FCR, and lymphoid organ weights for the overall study period of 42 d. With increased chromium dosage, the breast meat yield improved linearly (P = 0.045). Antibody response to Newcastle disease vaccination improved quadratically (P = 0.001) with increased dose of chromium in the diet. Improved cell-mediated immune response was indicated by the increase (quadratic, P = 0.00) in lymphocyte proliferation ratio with increased dose of chromium supplementation. Heterophil:lymphocyte ratio decreased (quadratic, P = 0.004) with chromium propionate dosage, suggestive of reduced stress levels. Chromium propionate supplementation also reduced serum glucose levels (quadratic, P = 0.008) and improved (quadratic, P = 0.016) the total protein levels.

Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme

Retrospective data suggests that low serum glucose levels during the treatment of glioblastoma multiforme (GBM) may improve clinical outcomes. As such, many patients are implementing a ketogenic diet (KD) in order to decrease serum glucose flux while simultaneously elevating circulating ketones during radiation therapy and chemotherapy for the treatment of GBM. With IRB approval, a retrospective review of patients with high-grade glioma treated with concurrent chemoradiotherapy and adjuvant chemotherapy was carried out from August 2010 to April 2013. Serum glucose and ketone levels, dexamethasone dose, and toxicity of patients undergoing a KD during treatment were also assessed. Blood glucose levels were compared between patients on an unspecified/standard diet and a KD. Toxicity was assessed by Common Terminology Criteria for Adverse Events version 4. In total, 53 patients were analyzed. Six underwent a KD during treatment. The diet was well tolerated with no grade III toxicity and one episode of grade II fatigue. No episodes of symptomatic hypoglycemia were experienced. Four patients are alive at a median follow-up of 14 months. The mean blood glucose of patients on a standard diet was 122 versus 84 mg/dl for those on a KD. Based on this retrospective study, a KD appears safe and well tolerated during the standard treatment of GBM. Dietary restriction of carbohydrates through a KD reduces serum glucose levels significantly, even in conjunction with high dose steroids, which may affect the response to standard treatment and prognosis. Larger prospective trials to confirm this relationship are warranted.

Anti-hyperglycemic and Anti-hyperlipemia Effects of Syzygium Cumini Seed in Alloxan Induced Diabetes mellitus in Swiss Albino Mice (Mus musculus)

Context: Syzygium cumini commonly known as jamun, a tree grown throughout India is used in traditional medication for the treatment of different diseases and ailments of human beings. Objective: In this study, the seed extract of Syzygium cumini was evaluated for anti-hyperlipidemic activity in alloxan induced diabetic mice. Materials and methods: LD50 and acute toxicity studies of Syzygium cumini (SC) were done. Hyperglycemia was induced in mice by alloxan. Three days after alloxan induction, the hyperglycemic mice were treated with Syzygium cumini orally at the dose of 150 and 250 mg/kg body weight daily for 21 days. After 21days of treatment, the animals were sacrificed and serum glucose and lipid profiles were estimated in the serum. Results: The LD50 was found to be 1000 mg/kg; 150 and 250 mg/kg doses were selected as no toxic symptoms were observed at both doses. SC significant (p<0.05) reduced serum glucose level, CH, TG-C, LDL-C, VLDL-C and increased HDL-C, body weight and liver, kidney weight. Conclusion: The above results prove potential of hypoglycemic and anti-hyperlipidemic activity Syzygium cumini.

Antidiabetic and antioxidative effect of jiang tang xiao ke granule in high-fat diet and low-dose streptozotocin induced diabetic rats.

Diabetes mellitus (DM), a kind of metabolic disease, is increasing over the last four decades in the world. The purpose of this study was to investigate the effect of Jiang Tang Xiao Ke (JTXK) granule, a naturally occurring ingredient from Chinese herbal medicines, on serum glucose, lipids, and oxidative stress in DM rats induced by high-fat diet and streptozotocin. JTXK granule 9 g/kg (based on crude herb equivalent) and pioglitazone 1.5 mg/kg (as a positive control for comparison) were orally administrated to DM rats for 4 weeks. Results showed that administration of JTXK granule reduced serum glucose, total cholesterol, triglyceride, and low density lipoprotein levels (by 12%, 33%, 57%, and 44%, resp.) but increased high-density lipoprotein level by 69%, compared with the drug-untreated DM rats. Serum malondialdehyde and nitric oxide levels were lowered (by 34% and 52%, resp.) associated with the elevation in serum superoxide dismutase levels (by 60%) after JTXK granule treatment. In addition, JTXK granule suppressed serum alanine aminotransferase activity (up to 50%) and alleviated pathological changes of pancreas and liver tissues in DM rats. The beneficial changes of pioglitazone on biomarkers were also found in DM rats. These findings suggested that JTXK granule may be an alternative medicine for the management of DM.

Novel Partial Agonist of PPAR-Gamma for Treatment of Diabetic Neuropathy in Rats

This work describes a novel ligand for peroxisome proliferator-activated receptor gamma (PPARgamma) and its hypoglycemic and analgesic activity in a murine model of diabetes-induced neuropathic pain. The molecular recognition of LASSBio-1772 by a PPARgamma binding domain showed that the compound is a partial agonist. Four weeks after male Wistar rats received a single intravenous injection of streptozotocin (STZ, 60 mg/kg), plasma glucose levels were increased from 92.5 ± 3.7 to 465.0 ± 21.6 mg/dL (P < 0.01) and serum insulin was reduced from 66.8 ± 7.8 to 25.5 ± 5.6 pmol/L (P<0.01). Diabetic animals were then, treated with either vehicle or LASSBio-1772 (50 mg/kg, i.p.) daily for 7 days. LASSBio-1772 significantly reduced blood glucose levels to 242.0 ± 55.1 mg/dL (P<0.05) and increased insulin levels to 58.7 ± 14.8 pmol/L (P<0.05), indicating the hypoglycemic activity of this compound. LASSBio-1772 also reduced the elevated triglyceride levels induced by STZ treatment from 74.1 ± 8.6 to 34.0 ± 6.3 mg/dL (P<0.01). LASSBio-1772 could reduce serum glucose levels via increased insulin levels and potentially improve insulin sensitivity. Neuropathy was detected after four weeks of STZ-induced diabetes, with reduced thermal heat withdrawal latency from 11.7 ± 0.1 to 7.1 ± 0.2 s (P<0.01) and paw withdrawal threshold from 37.5 ± 2.1 to 29.9 ± 1.1 g (P<0.05) indicating the establishment of hyperalgesia and allodynia. LASSBio-1772 treatment restored both measures to non-diabetic values (12.2 ± 0.4 s and 34.5 ± 1.5 g). In conclusion, treatment with LASSBio-1772, a partial PPARgamma agonist, decreased hyperglycemia and neuropathic pain induced by diabetes. PPARgamma stimulation by LASSBio-1772 could prevent inflammation and inhibit both peripheral and central sensitization.

Ameliorative Effect of Hexane Extract of Phalaris canariensis on High Fat Diet‐Induced Obese and Streptozotocin‐Induced Diabetic Mice

Obesity is one of the major factors to increase various disorders like diabetes. The present paper emphasizes study related to the antiobesity effect of Phalaris canariensis seeds hexane extract (Al-H) in high-fat diet- (HFD-) induced obese CD1 mice and in streptozotocin-induced mild diabetic (MD) and severely diabetic (SD) mice.AL-H was orally administered to MD and SD mice at a dose of 400 mg/kg once a day for 30 days, and a set of biochemical parameters were studied: glucose, cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, ALP, SGOT, SGPT, glucose-6-phosphatase, glucokinase, hexokinase, SOD, CAT, GSH, GPX activities, and the effect on insulin level. HS-H significantly reduced the intake of food and water and body weight loss as well as levels of blood glucose, serum cholesterol, triglyceride, lipoprotein, oxidative stress, showed a protective hepatic effect, and increased HDL-cholesterol, serum insulin in diabetic mice. The mice fed on the high-fat diet and treated with AL-H showed inhibitory activity on the lipid metabolism decreasing body weight and weight of the liver and visceral adipose tissues and cholesterol and triglycerides in the liver. We conclude that AL-H can efficiently reduce serum glucose and inhibit insulin resistance, lipid abnormalities, and oxidative stress in MD and SD mice. Our results demonstrate an antiobesity effect reducing lipid droplet accumulation in the liver, indicating that its therapeutic properties may be due to the interaction plant components soluble in the hexane extract, with any of the multiple targets involved in obesity and diabetes pathogenesis.

Effects of oregano or red pepper essential oil supplementation to diets for broiler chicks with delayed feeding after hatching. 1. Performance and microbial population

SUMMARY This study was conducted to investigate the effects of dietary supplementation of oregano or red pepper essential oil on the performance, digestive organs, serum biochemistry parameters, and microbial population of the small intestine of broilers with immediate, or 24- or 48-h posthatching delayed access to diet and water. The dietary treatments included (1) a nonsupplemented corn-soybean meal diet (CONT), (2) CONT + 250 mg/kg of oregano essential oil (OO250), and (3) CONT + 250 mg/kg of red pepper essential oil (RPO250). Irrespective of dietary treatment, especially delayed access to diet and water for 48 h posthatch significantly decreased daily BW gain from 0 to 21 d and daily feed intake from 4 to 21 d and increased the relative weight of the yolk sac at 3 d of broilers. The relative weight of the liver or gizzard of chickens at 21 d was significantly decreased by delayed access to diet and water for 24 h posthatch. The diet containing RPO250 significantly increased the relative weight of the pancreas at 21 d. Delayed access to diet and water for 24 or 48 h posthatch significantly reduced serum glucose levels at 21 d. The serum aspartate aminotransferase level in broilers given immediate access to feed and water was significantly decreased by the diet containing RPO250. Generally, the coliform bacteria and total yeast contents of the small intestine of chickens were significantly increased by extending the time to access to feed and water for broilers. Total aerobic bacteria contents of the small intestine of broilers with immediate, or 24- or 48-h posthatching delayed access to diet and water was significantly decreased by CONT, OO250, and RPO250 diets.

Myrciaria caulifloraPeel Flour Had a Hypolipidemic Effect in Rats Fed a Moderately High-Fat Diet

The aim of this study was to evaluate the hypolipidemic effects of Myrciaria cauliflora peel flour (MPF) in rats. Previously, it was determined the proximate composition, total phenolics, and anthocyanins of MPF. Then, groups of male rats were randomly assigned to one of the five treatment groups. The standard group received a basal diet as recommended by the American Institute of Nutrition (AIN93M). The control group (CTRL) received the AIN93M diet, which added 7% of pork lard. The jaboticaba groups had their diets similar to CTRL, but added MPF at 7 (JAB1), 10 (JAB2), or 15% (JAB3). Serum and liver cholesterol as well as serum levels of high-density lipoprotein (HDL), triglycerides (TG), and glucose were evaluated. Fecal output of lipids was also measured. MPF had expressive amounts of fibers (25.28±2.52 g/100 g), total phenolics (18.95±5.27 mg/100 g), and anthocyanins (6.82±0.18 mg/100 g). The inclusion of the MPF at three ratios, reduced serum cholesterol and TG compared with CTRL. JAB3 raised serum HDL and reduced liver cholesterol compared with CTRL. JAB3 and JAB2 reduced serum glucose compared with CTRL. JAB groups eliminated more feces and had pH values lower than CTRL. However, there was no difference in lipid fecal output between all groups. MPF has a hypolipidemic potential, especially on reducing serum cholesterol and TG. These effects can be attributed, at least in part, to its fiber and phenolic composition.

Potent Anti-Diabetic Effects of MHY908, a Newly Synthesized PPAR α/γ Dual Agonist in db/db Mice

Peroxisome proliferator-activated receptor (PPAR) α/γ dual agonists have been developed to alleviate metabolic disorders and have the potential to be used as therapeutic agents for the treatment of type 2 diabetes. In this study, we investigated the effects of a newly synthesized PPAR α/γ dual agonist, 2-[4-(5-chlorobenzo [d] thiazol-2-yl) phenoxy]-2-methylpropanoic acid (MHY908) on type 2 diabetes in vitro and in vivo. To obtain initial evidence that MHY908 acts as a PPAR α/γ dual agonist, ChIP and reporter gene assays were conducted in AC2F rat liver cells, and to investigate the anti-diabetic effects and molecular mechanisms, eight-week-old, male db/db mice were allowed to eat ad libitum, placed on calorie restriction, or administered MHY908 (1 mg or 3 mg/kg/day) mixed in food for 4 weeks. Age-matched male db/m lean mice served as non-diabetic controls. It was found that MHY908 enhanced the binding and transcriptional activity of PPAR α and γ in AC2F cells, and it reduced serum glucose, triglyceride, and insulin levels, however increased adiponectin levels without body weight gain. In addition, MHY908 significantly improved hepatic steatosis by enhancing CPT-1 levels. Remarkably, MHY908 reduced endoplasmic reticulum (ER) stress and c-Jun N-terminal kinase (JNK) activation in the livers of db/db mice, and subsequently reduced insulin resistance. The study shows MHY908 has beneficial effects on type 2 diabetes by simultaneously activating PPAR α/γ and improving ER stress, and suggests that MHY908 could have a potent anti-diabetic effect as a PPAR α/γ dual agonist, and potential for the treatment of type 2 diabetes.

The proarrhythmic effect of hypoglycemia: evidence for increased risk from ischemia and bradycardia

Hypoglycemia increases the risk for both overall and sudden death. At a cellular level, hypoglycemia causes alterations in the physiology of myocardial tissue that are identical to proarrhythmic medications. Reduced serum glucose blocks the repolarizing K(+) channel HERG, which leads to action potential and QT prolongation and is uniformly associated with risk for torsades de pointes ventricular tachycardia. The sympathetic response induced by hypoglycemia also increases the risk of arrhythmias from Ca(2+) overload, which occur with sympathomimetic medications and excessive beta adrenergic stimulation. Thus, hypoglycemia can be considered a proarrhythmic event. This review focuses on emerging evidence for two other important changes induced by hypoglycemia that promote arrhythmias: ischemia and bradycardia. Studies of patients with "insulin shock" therapy from the early twentieth century and other more recent data strongly suggest that hypoglycemia can cause ischemia of myocardial tissue, both in association with coronary artery obstructions and by cellular mechanisms. Ischemia induces multiple proarrhythmic responses. Since ischemia itself reduces the possibility of using energy substrates other than glucose, hypoglycemia may generate positive feedback for electrophyisologic destabilization. Recent studies also show that hypoglycemia can cause bradycardia and heart block. Bradycardia is known to cause action potential prolongation and potentiate the development of torsades de pointes, particularly with low-serum K(+) which can be induced by hypoglycemic episodes. Thus, hypoglycemia-induced bradycardia may also create a dynamic, positive feedback for the development of arrhythmias and sudden death. These studies further support the hypothesis that hypoglycemia is a proarrhythmic event.

Quality and Biochemical Influence of Eugenol to Anesthetize Crucian Carp (Carassius Auratus)

The aim of this study was to identify the influence of the anesthetic eugenol on crucian carp. The muscle quality and freshness were little influenced by anesthesia from the perspective of cooking loss (CL) and total volatile basic nitrogen (TVB-N). In contrast, lower redness, liquid loss (LL), and 2-thiobarbituric acid (TBA) values were observed in anesthetized fish. It was found that anesthesia increased serum cortisol content and reduced serum glucose concentration. There was little influence of eugenol on serum glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), and alkaline phosphatase (AKP) activities, while serum and muscle acid phosphatase (ACP) activities significantly increased after the use of the anesthetic. Results suggested that the stress of eugenol to crucian carp was nontoxic and did not lead to hyperglycemia. On the basis of these findings, eugenol as an anesthetic is effective and safe for the transportation of crucian carp.

The effect of cinnamon on glucose control in patients with type 2 diabetes mellitus in Pontianak, Indonesia

The objective of this study was to examine pre- and post-glucose serum concentration levels in diabetes mellitus patients after the administration of cinnamon powder. A quasi-experimentaldesign was done with 40 patients, with pre- and post-test non-equivalent control groups, without randomization. The first group was given a cinnamon powder extract solution to be taken 3 times per day and designated as the experimental group. The dose amounted to 3 g of cinnamon spread over the day, after breakfast, lunch, and dinner, respectively. The subjects were instructed to take the 3 g of cinnamon immediately following their meals. The patients with type 2 diabetes in theintervention group were aged 54.4 ± 8.7 years, and in the control group were aged 56.2 ± 10.5 years. There was a significant difference between the pre- and post-serum glucose concentrationtests between the two groups. The measurements for the intervention group were 311.4 ± 96 and 185.8 ± 21, respectively (p = 0.000), while the control group pre-test was 277.1 ± 74, and the post-test was 205.3 ± 45 (p = 0.003). The results of this study demonstrated that intake of cinnamon reduces serum glucose in type 2 diabetes. Key words: Cinnamon, diabetes mellitus, blood glucose.

Theflavins and Theasinensin A Derived from Fermented Tea Have Antihyperglycemic and Hypotriacylglycerolemic Effects in KK-Ay Mice and Sprague–Dawley Rats

Although tea polyphenols are reported to improve serum glucose and lipid levels by inhibiting amylase activity and reducing lipid absorption, in vivo data are lacking. We evaluated in vivo the antihyperglycemic and hypotriacylglycerolemic effects of theaflavins (TFs) and theasinensin A (TSA) refined from fermented tea to purities of 12 and 59%, respectively. Feeding male KK-A(y) mice diets with 0.1% TFs or TSA for 6 weeks reduced serum glucose levels by >30% compared to a control diet. Rats fed diets containing 0.2% TFs or TSA for 4 weeks had higher fecal fat excretion and 33% lower hepatic triacylglycerol; hepatic fatty acid synthase activity was not affected. Oral administration of TFs or TSA reduced the increase in serum triacylglycerol after an oral bolus of a fat emulsion. These results indicate TFs and TSA induce antihyperglycemic responses in diabetic mice and are hypotriacylglycerolemic in rats by suppressing intestinal fat absorption.

CHANGES IN SERUM GLUCOSE AND LIPID PROFILE AS INTRAOCULAR PRESSURE BIOMARKERS IN PLASMODIUM BERGHEI INFECTED MICE TREATED WITH AQUEOUS LEAF EXTRACT OF NAUCLEA LATIFOLIA

Nauclea latifolia has been shown to have hypocholesterolaemic and hypoglycaemic effect, and cholesterol and glucose have been implicated to play significant roles in the pathogenesis of glaucoma. This study investigates the serum glucose and lipid profile of Plasmodium berghei infected mice treated with aqueous leaf extract of Nauclea latifolia. Adult albino male mice, 8 weeks old, weighing 12g-25g and divided into 6 groups of 5 mice per group were used for the experiment. Mice were inoculated intraperitoneally with 0.1ml parasitized blood suspension and parasitaemia assessed by thin blood films stained with Geimsa stain. Aqueous leaf extract of Nauclea latifolia was orally administered at different doses (200mg/kg. body weight and 300mg/kg body weight daily) to both normal and P. berghei infected mice for a period of 4 days. Serum glucose, triglyceride, high density lipoprotein and cholesterol levels were estimated. Significant (p<0.05) reduction in serum glucose and cholesterol was revealed in the untreated parasitized control when compared with other groups but no significant change (p<0.05) in serum triglyceride and high density lipoprotein were observed in parasitized control when compared with normal control mice. However, oral administration of Nauclea latifolia significantly (p<0.05) maintained the cholesterol and glucose levels in the infected mice toward the normal value when compared with the untreated parasitized mice with no significant change in the triglyceride and high density lipoprotein levels. These results suggest that aqueous extract of Nauclea latifolia may not cause or lead to the increase in the intraocular pressure (glaucoma) both in normal and malaria infected mice.

Effect of Spironolactone on Cardiovascular Complications Associated with Type-2 Diabetes in Rats

We have studied the effect spironolactone (20 mg/kg/day) on cardiovascular complications in neonatal model of diabetes in rats, induced by administering 90 mg/kg streptozotocin (STZ), i.p. in 2 day old rats. Diabetes was checked after 12 weeks. At the end of 8 weeks of treatment, various biochemical and cardiac parameters were measured. STZ produced hyperglycemia, hyperinsulinemia, dyslipidemia, increased creatinine, cardiac enzyme and C-reactive protein (CRP) levels, worsened hemodynamic parameters, cardiac hypertrophy and oxidative stress. Chronic treatment with spironolactone significantly reduced serum glucose levels but did not alter insulin levels. It also significantly prevented the dyslipidemia and reduced elevated Lactate de-hydrogenase, creatinine kinase, CRP and creatinine levels. Chronic treatment with spironolactone prevented STZ-induced hypertension, tachycardia and elevated rate of pressure development and decay. Spironolactone also produced beneficial effect by preventing cardiac hypertrophy as evident from left ventricular collagen levels, cardiac and left ventricular hypertrophic indices and prevented oxidative stress. In conclusion, our data suggests that spironolactone prevents STZ induced metabolic abnormalities and cardiovascular complications in animal model of type 2 diabetes.

SYNTHESIS OF SOME NEW DERIVATIVES OF ISOINDOLINE-1,3-DIONE NUCLEUS FOR ANTIHYPERGLYCEMIC EVALUATION

In order to produce potent new leads for antidiabetic drugs, a new series of isoindoline-1,3-dione analogues bearing aryl sulfonylurea moieties were synthesized and screened for their antihyperglycemic activity. Some of newly synthesized compounds were identified as active antihyperglycemic agents. Compounds N-(cyclohexylcarbamoyl)-4-[2-(1,3-dioxoisoindolin-2-yl) ethyl]benzenesulfon-amide(VIIo),N-(cyclopentylcabamoyl)-4-[2-(1,3-dioxoiso- indolin-2-yl)ethyl] benzene sulfonamide (VIIp), N-(butylcabamoyl)-4-[2-(1,3-dioxoisoindolin-2-yl)ethyl]benzenesulfonamide(VIIq),N-(cyclohexylcarbamoyl) -4- [ ( 1, 3- dioxo - isoindolin- 2 – yl ) methyl ] benzenesulfonamide (VIIh) and N-(propylcabamoyl)-4-[2-(1,3-dioxoisoindolin-2-yl)ethyl]benzenesulfonamide (VIIr) proved to be the most active members of this study, as compered to to the reference gliclazide. They showed serum glucose reduction values of 52%, 48% 45%, 44% and 44%, respectively. The detailed synthesis and biological screening data are reported.

Hypoglycemic Activity of Methanolic Fruit Pulp Extract of &lt;em&gt;Adansonia digitata&lt;/em&gt; on Blood Glucose Levels of Alloxan Induced Diabetic Rats

This study was carried out to evaluate the hypoglycemic properties of the methanolic extract of Adansonia digitata fruit pulp on blood glucose. Forty eight of the rats were randomly distributed into six. Group one served as the normal control and Group two rats were administered with alloxan (150 mg/kg) intraperitoneally and served as the diabetic control. Groups 3, 4 and 5 were intraperitoneally administered with alloxan (150 mg/kg) and orally administered with methanolic extract of Adansonia digitata fruit pulp (100, 200 and 300 mg/kg) once daily for 4weeks. Group six rats were intraperitoneally administered with alloxan (150 mg/kg) and orally administered with chlorpropamide (84 mg/kg) once daily for 4 weeks. The serum concentration of glucose of all the rats in each group was determined after the 14 th and 28 th dose of treatment. There was significant (p<0.001) reduction of serum glucose in the three groups of rats administered with methanolic extract of Adansonia digitata fruit pulp at second and fourth week of the treatment. The group of animal treated with chlorpropamide (84 mg/kg) also showed significant (p<0.001) reduction of serum glucose compared to most effective dose of the methanolic extract (300 mg/kg) during the second and fourth week of the treatment. The result of qualitative phytochemical analysis of methanolic extract of Adansonia digitata fruit pulp indicated the presence of glycosides, flavonoids, tannins, saponins, terpenoids and steroids. This result suggests that the methanolic fruit pulp extract of Adansonia digitata possess antidiabetic effect on alloxan induced diabetic rats.

Naproxen and Cromolyn as New Glycogen Synthase Kinase 3β Inhibitors for Amelioration of Diabetes and Obesity: An Investigation by Docking Simulation and Subsequent In Vitro/In Vivo Biochemical Evaluation

Naproxen and cromolyn were investigated as new inhibitors of glycogen synthase kinase-3β (GSK-3β) in an attempt to explain their hypoglycemic properties. Study included simulated docking experiments, in vitro enzyme inhibition assay, and in vivo validations. Both drugs not only were optimally fitted within a GSK-3β binding pocket via several attractive interactions with key amino acids but also exhibited potent in vitro enzymatic inhibitory activities of IC50 1.5 and 2.0 µM for naproxen and cromolyn, respectively. In vivo experiments illustrated that both drugs significantly reduced serum glucose and increased hepatic glycogen- and serum insulin levels in normal and type II diabetic Balb/c mice models. In obese animal model, both drugs exhibited significant reduction in mice weights, serum glucose, and resistin levels along with significant elevation in serum insulin, C-peptide, and adiponectin values. It can be concluded that naproxen and cromolyn are novel GSK-3β inhibitors and can help in management of diabetes and obesity.