Reduced Serum Glucose Research Articles

Novel PLGA-based nanoparticles for the oral delivery of insulin

BackgroundInsulin is the drug therapy for patients with insulin-dependent diabetes mellitus. A number of attempts have been made in the past to overcome the problems associated with the oral delivery of insulin, but with little success. Orally administered insulin has encountered with many difficulties such as rapid degradation and poor intestinal absorption. The potential use of D-α-tocopherol poly(ethylene glycol) 1000 succinate (TPGS)-emulsified poly(ethylene glycol) (PEG)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was investigated for sustained delivery of insulin (IS).ObjectiveTo investigate the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs) as a potential drug carrier for the oral delivery of insulin.MethodsA series of biodegradable low-molecular-weight PLGA (80/20 [PLG4] and 70/30 [PLG6]) copolymers were synthesized by melt polycondensation. The commercial insulin-loaded TPGS-emulsified PEG-capped PLGA NPs (ISTPPLG NPs) were synthesized by water–oil–water emulsion solvent evaporation method. The physical and chemical properties of PLGA copolymers, particle size, zeta potential, and morphology of the NPs were examined. The in vivo studies of ISTPPLG NPs were carried out in diabetic rats by oral administration.ResultsThe maximum encapsulation efficiency of ISTPPLG6 NPs was 78.6%±1.2%, and the mean diameter of the NPs was 180±20 nm. The serum glucose level was significantly (twofold) decreased on treatment with ISTPPLG NPs, and there was a threefold decrease with insulin-loaded PLGA (70/30) NPs when compared to that of free insulin-treated diabetic rats. The results show that the oral administration of ISTPPLG6 NPs is an effective method of reducing serum glucose level for a period of 24 hours. Histopathological studies reveal that ISTPPLG NPs could restore the damage caused by streptozotocin in the liver, kidneys, and pancreas, indicating its biocompatibility and regenerative effects.ConclusionISTPPLG6 NPs can act as potential drug carriers for the oral delivery of insulin.

Abstract T P96: Controlled Brain Glucose Uptake and Metabolism by Ethanol: An Alternative Approach in Improving Stroke Outcome

Introduction: Post-stroke oxygen deficit impairs oxidative phosphorylation of glucose. Surviving brain cells increase anaerobic glycolysis (hyperglycolysis) promoting reactive oxygen species (ROS) synthesis via lactic acidosis and NADPH oxidase (NOX) activation. Hyperglycemia present in 40% of stroke patients with or without diabetes perpetuates hyperglycolysis. Insulin, the only treatment to attenuate hyperglycemia-induced hyperglycolysis, is linked to increased risk of hypoglycemia and mortality. We showed that EtOH reduced ROS-mediated brain damage. Here, we studied whether hyperglycemia/hyperglycolysis-enhanced brain injury are ameliorated by reducing brain glucose uptake and metabolism rather than affecting blood glucose levels. Methods: Sprague-Dawley rats underwent a 2 h right middle cerebral artery occlusion (MCAO). EtOH (1.5 g/kg) or saline was injected IP upon reperfusion, then sacrificed 3 and 24 h later. Energy stores, hyperglycolysis-associated glucose uptake and metabolism, lactic acidosis, and oxidative stress were assessed via ADP/ATP ratio, NAD+/NADH ratio, Na+/K+ ATPase activity, levels of brain and blood glucose, glucose transporter GLUT 1 and 3, lactate, lactate dehydrogenase (LDH), ROS, phosphofructokinase-1 (PFK-1), NOX, and PFK-1 and NOX activity. Results: Ischemic rats showed significant (p<0.01) increase in ADP/ATP and NAD+/NADH ratios, and decrease in Na+/K+ ATPase activity indicating impaired metabolic and neural activity. Increased blood glucose and decreased brain glucose indicate hyperglycemic condition with hyperglycolysis. High levels of GLUT 1 and 3, lactate, LDH , PFK-1, NOX, and ROS support ROS associated hyperglycolysis. EtOH normalized these metabolic parameters to control levels, but only blood glucose remained higher. In sum, EtOH attenuates hyperglycemia-enhance brain injury by reducing glucose uptake and its hyperglycolytic-mediated metabolism under hyperglycemic condition. Conclusion: EtOH administered upon reperfusion is neuroprotective against ROS-mediated brain damage in acute ischemic stroke. It attenuates hyperglycemia-enhanced hyperglycolysis at the level of glucose uptake, utilization, and metabolism rather than reducing serum glucose levels.

Effect of Hibiscus rosa sinensis L. basic leaf extract fraction on type-1 diabetic animal model

Type 1 diabetes mellitus (T1DM) results when pancreatic β-cells are destroyed or absent, leading to decrease in insulin production and secretion. The objective of the present investigation is to screen one of the isolated fractions of Hibiscus rosa sinensis on type-1 diabetic animal model for antidiabetic activity. Experiment was conducted by dissolving basic leaf extract fraction in tween-80 (1%) with two concentrations of 100 and 200 mg/kg body weight and feed orally to Non Obese Diabetic (NOD) mice. After oral feeding of basic leaf fraction there was a significant reduction in serum glucose, glycosylated haemoglobin, triglycerides, cholesterol, blood urea in the diabetic animal model. There was enhancement in HDL and liver glycogen compared to control diabetic animal. Basic leaf fraction has demonstrated significant antidiabetic properties on type-1 animal model by enhancing insulin secretion.

The Effect of Melatonin on Gastric Parameters Following Diabetes Induction in Male Rats

Background. Gastrointestinal complaints are common among diabetic patients. The gastrointestinal tract contains melatonin. The binding sites of melatonin have been identified in all GIT tissues. Melatonin can modify activities of the gut and liver. The aim of this study was to evaluate the possible protective effects of melatonin against gastric motility and secretary responses in Streptozotocin-induced diabetes in rats. Methods. Streptozotocin was injected intraperitoneally at a single dose of 60 mg/kg for diabetes induction. One week after inducing diabetes, Melatonin (5, 10, 20 mg/kg/day, IP.) was injected for 14 days. Gastric acid and mucus were measured in all animals by chemical methods. Gastric motility was investigated by powerlab system. Results. Streptozotocin induced a significant increase in blood glucose levels (p<0.001) and significant decrease in gastric acid, mucus, motility and body weight in diabetic groups. Treatment of diabetic rats with melatonin significantly reduced blood glucose (p<0.001) and increased gastric mucus (p<0.001) and motility (p<0.01 and p<0.05 in groups 4 and 5 respectively) with no effect on body weight and gastric acid concentration. Conclusion. These data suggested that melatonin treatment has a therapeutic effect on diabetic gastrointestinal disturbances by reduction of serum glucose and increasing gastric motility and gastric mucus levels, but no effect on gastric acid and body weight. © 2015, Acta Endocrinologica Foundation. All rights reserved.

Sea cucumber cerebrosides and long-chain bases from Acaudina molpadioides protect against high fat diet-induced metabolic disorders in mice.

Metabolic syndrome (MS) is a cluster of metabolic disorders such as abdominal obesity, hypertension, glucose intolerance, dyslipidemia and hepatic steatosis that contribute to increased cardiovascular morbidity and mortality. There is an urgent need for strategies to prevent this emerging global epidemic. Recently, growing interest in discovering food functional nutrients for the prevention and treatment of MS has generated. In the present study, sea cucumber cerebrosides (SCC) and the main structural units, long-chain bases (LCB), were prepared from Acaudina molpadioides and then administered to high fat (HF) diet-induced obese C57BL/6J mice at a diet supplement dosage of 0.025% for 5 weeks to evaluate their effects on obesity-related metabolic disorders. SCC and LCB significantly decreased epididymal adipose tissue weights, lowered hepatic triacylglycerol levels, and reduced serum glucose, insulin levels and HOMA-IR index in mice. The activities of hepatic lipogenetic enzymes including FAS, ME and the mRNA levels of SREBP-1c and FAS were reduced by SCC and LCB treatment. However, SCC and LCB showed no effect on the hepatic lipolysis pathway. Besides, SCC and LCB also efficiently up-regulated the gene expression of SREBP-1c, FAS, ACC, ATGL and HSL, and down-regulated the gene expression of LPL and VLDL-r in the adipose tissue. These results demonstrated that SCC and LCB were efficacious in suppressing hepatic SREBP-1c mediated lipogenesis, inhibiting lipid uptake and increasing TG catabolism in the adipose tissue. The ameliorative degree and regulatory mechanisms of these two compounds were basically the same, suggesting that LCB are the key active structural units. Such findings would offer new insight into the application of SCC or LCB in the development of functional foods for preventing MS in humans.

A high-fat diet modulates iron metabolism but does not promote liver fibrosis in hemochromatotic Hjv⁻/⁻ mice.

Hemojuvelin (Hjv) is a membrane protein that controls body iron metabolism by enhancing signaling to hepcidin. Hjv mutations cause juvenile hemochromatosis, a disease of systemic iron overload. Excessive iron accumulation in the liver progressively leads to inflammation and disease, such as fibrosis, cirrhosis, or hepatocellular cancer. Fatty liver (steatosis) may also progress to inflammation (steatohepatitis) and liver disease, and iron is considered as pathogenic cofactor. The aim of this study was to investigate the pathological implications of parenchymal iron overload due to Hjv ablation in the fatty liver. Wild-type (WT) and Hjv(-/-) mice on C57BL/6 background were fed a standard chow, a high-fat diet (HFD), or a HFD supplemented with 2% carbonyl iron (HFD+Fe) for 12 wk. The animals were analyzed for iron and lipid metabolism. As expected, all Hjv(-/-) mice manifested higher serum and hepatic iron and diminished hepcidin levels compared with WT controls. The HFD reduced iron indexes and promoted liver steatosis in both WT and Hjv(-/-) mice. Notably, steatosis was attenuated in Hjv(-/-) mice on the HFD+Fe regimen. Hjv(-/-) animals gained less body weight and exhibited reduced serum glucose and cholesterol levels. Histological and ultrastructural analysis revealed absence of iron-induced inflammation or liver fibrosis despite early signs of liver injury (expression of α-smooth muscle actin). We conclude that parenchymal hepatic iron overload does not suffice to trigger progression of liver steatosis to steatohepatitis or fibrosis in C57BL/6 mice.

Serum glucose and risk of cancer: a meta-analysis.

BackgroundRaised serum glucose has been linked to increased risk of many solid cancers. We performed a meta-analysis to quantify and summarise the evidence for this link.MethodsPubmed and Embase were reviewed, using search terms representing serum glucose and cancer. Inclusion and exclusion criteria focused on epidemiological studies with clear definitions of serum glucose levels, cancer type, as well as well-described statistical methods with sufficient data available. We used 6.1 mmol/L as the cut-off for high glucose, consistent with the WHO definition of metabolic syndrome. Random effects analyses were performed to estimate the pooled relative risk (RR).ResultsNineteen studies were included in the primary analysis, which showed a pooled RR of 1.32 (95% CI: 1.20 – 1.45). Including only those individuals with fasting glucose measurements did not have a large effect on the pooled RR (1.32 (95% CI: 1.11-1.57). A stratified analysis showed a pooled RR of 1.34 (95% CI: 1.02-1.77) for hormonally driven cancer and 1.21 (95% CI: 1.09-1.36) for cancers thought to be driven by Insulin Growth Factor-1.ConclusionA positive association between serum glucose and risk of cancer was found. The underlying biological mechanisms remain to be elucidated but our subgroup analyses suggest that the insulin- IGF-1 axis does not fully explain the association. These findings are of public health importance as measures to reduce serum glucose via lifestyle and dietary changes could be implemented in the context of cancer mortality.

Protective effect of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats

Mulberry leaves (Morus alba L.) are a traditional Chinese medicine for blood serum glucose reduction. This study evaluated the protective effects of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats. In this study, 80 Sprague-Dawley rats were divided into five groups: A (control), B (diabetic treated with saline), C-D (diabetic treated with 0.3, 0.1 g/kg mulberry flavonoids once a day for 8 weeks) and E (diabetic treated with 0.3 mg/kg methycobal). The diabetic condition was induced by intraperitoneal injection of 200 mg/kg alloxan dissolved in saline. At the end of the experimental period, blood, and tissue samples were obtained for biochemical and histopathological investigation. Treatment with 0.3 g/kg mulberry flavonoids significantly inhibited the elevated serum glucose (P&lt; 0.01). The increased myelin sheath area (P&lt; 0.01), myelinated fiber cross-sectional area and extramedullary fiber number (P&lt; 0.05) were also reduced in alloxan-induced rats treated with 0.3 g/kg mulberry flavonoids. 0.3 g/kg mulberry flavonoids also markedly decreased onion-bulb type myelin destruction and degenerative changes of mitochondria and Schwann cells. These findings demonstrate that mulberry flavonoids may improve the recovery of a severe peripheral nerve injury in alloxan-induced diabetic rats and is likely to be useful as a potential treatment on peripheral neuropathy (PN) in diabetic rats.

Histone deacetylase inhibitor, trichostatin A, improves learning and memory in high-fat diet-induced cognitive deficits in mice.

Metabolic syndrome is increasingly recognized for its effects on cognitive health. Recent studies have highlighted the role of histone deacetylases (HDACs) in metabolic syndrome and cognitive functions. The present study was designed to investigate the possible therapeutic role of a HDAC inhibitor, trichostatin A (TSA), in cognitive impairment associated with metabolic syndrome. To ascertain the mechanisms involved, we fed mice with high-fat diet (HFD) for 4 weeks and examined changes in behavioral and biochemical/oxidative stress markers. Mice subjected to HFD exhibited characteristic features of metabolic disorder, viz., hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and lower high-density lipoprotein (HDL) cholesterol levels. Moreover, these mice showed severe deficits in learning and memory as assessed by the Morris water maze and passive avoidance tasks along with elevated oxidative stress and inflammatory markers in brain homogenates. The observed changes occurred concurrently with reduced brain-derived neurotrophic factor (BDNF). In contrast, the mice treated with the HDAC inhibitor, TSA (0.5 and 1 mg/kg, i.p.), showed a significant and dose-dependent reduction in serum glucose, triglycerides, and total cholesterol along with improvement in HDL-cholesterol levels and learning and memory performance. TSA treatment also results in alleviation of oxidative stress and neuroinflammatory markers. Moreover, TSA significantly augmented the BDNF levels in HFD-fed mice. Thus, based upon these observations, it may be suggested that HDAC inhibition could be a novel therapeutic strategy to combat cognitive impairment associated with metabolic syndrome.

Adaptogenic Activity of Lyophilized Hydroethanol Extract of Pandanus odoratissimus in Swiss Albino Mice.

Background. The leaves of Pandanus odoratissimus Linn have been widely used in Ayurveda to treat a variety of common and stress related disorders. In the present investigation, hydroethanol extract of leaves of Pandanus odoratissimus Linn (LEPO) were evaluated for antistress activity in normal and stress induced mice. Furthermore, the extract was studied for nootropic (adaptogenic) activity in mice and in vitro antioxidant potential to correlate with its adaptogenic and antistress activity. LEPO (100 and 200 mg/kg p.o) was evaluated against forced swimming endurance stress test, anoxia stress tolerance and immobilization stress and chronic cold resistant stress tests, and biomarkers (serum glucose, Corticosterone, WBC, RBC, and DLC count) to assess the antistress activity in mice. Withania somnifera (WS) (100 mg/kg p.o) was selected as reference standard. The parameters like anoxia stress tolerance time were recorded in anoxia stress and estimation of biochemical marker levels and determination of organs weight were carried out in immobilization stress models. Results. Concomitant treatment with LEPO 200 mg/kg significantly increased in anoxia stress tolerance time. Dose dependent significant reduction in serum glucose, corticosterone, and WBC, RBC, and DLC was observed in immobilisation stress model as compared to stressed group. LEOP 200 mg/kg and WS 100 mg/kg significantly reversed/inhibited the stress induced changes in these parameters. The results from the present study indicate that these values also express that dose dependent significant adaptogenic activity in stressed animals. Conclusion. The present study provides scientific support for the antistress (adaptogenic) and nootropic activities of lyophilized hydroethanol extract of Pandanus odoratissimus Linn and substantiate the traditional claims for the usage of Pandanus in stress induced disorders.

Dietary stearic acid leads to a reduction of visceral adipose tissue in athymic nude mice.

Stearic acid (C18:0) is a long chain dietary saturated fatty acid that has been shown to reduce metastatic tumor burden. Based on preliminary observations and the growing evidence that visceral fat is related to metastasis and decreased survival, we hypothesized that dietary stearic acid may reduce visceral fat. Athymic nude mice, which are used in models of human breast cancer metastasis, were fed a stearic acid, linoleic acid (safflower oil), or oleic acid (corn oil) enriched diet or a low fat diet ad libitum. Total body weight did not differ significantly between dietary groups over the course of the experiment. However visceral fat was reduced by ∼70% in the stearic acid fed group compared to other diets. In contrast total body fat was only slightly reduced in the stearic acid diet fed mice when measured by dual-energy x-ray absorptiometry and quantitative magnetic resonance. Lean body mass was increased in the stearic acid fed group compared to all other groups by dual-energy x-ray absorptiometry. Dietary stearic acid significantly reduced serum glucose compared to all other diets and increased monocyte chemotactic protein-1 (MCP-1) compared to the low fat control. The low fat control diet had increased serum leptin compared to all other diets. To investigate possible mechanisms whereby stearic acid reduced visceral fat we used 3T3L1 fibroblasts/preadipocytes. Stearic acid had no direct effects on the process of differentiation or on the viability of mature adipocytes. However, unlike oleic acid and linoleic acid, stearic acid caused increased apoptosis (programmed cell death) and cytotoxicity in preadipocytes. The apoptosis was, at least in part, due to increased caspase-3 activity and was associated with decreased cellular inhibitor of apoptosis protein-2 (cIAP2) and increased Bax gene expression. In conclusion, dietary stearic acid leads to dramatically reduced visceral fat likely by causing the apoptosis of preadipocytes.

Anti-diabetic properties of Daphniphyllum macropodum fruit and its active compound.

We evaluated in vitro anti-diabetic activities of 497 native plants of Jeju Island (South Korea) by measuring the induction of adipocyte differentiation. Among the plants, Daphniphyllum macropodum fruit extract (DME) had the highest peroxisome proliferator-activated receptor γ (PPARγ) agonist activity and was therefore selected as a potential source of anti-diabetic agents. To elucidate the active components of DME, constituent compounds were purified and their effects on the adipocyte differentiation were studied. Using activity-guided fractionation, four compounds were isolated from DME and their adipogenic effects were evaluated. Among the compounds isolated, 5,7-dihydroxychromone potently induced the differentiation of mouse 3T3-L1 preadipocytes. DME and 5,7-dihydroxychromone increased PPARγ and liver X receptor α (LXRα) mRNA expression levels. To determine whether the adipogenic effects we observed might affect serum glucose levels, we undertook in vivo experiment using streptozotocin-/high-fat diet-induced type 2 diabetes mouse model. DME supplementation reduced serum glucose, total cholesterol, and triacylglycerol levels in diabetes mice. These results suggest that DME may be useful for the prevention and treatment of type 2 diabetes mellitus. Moreover, it was proposed that 5,7-dihydroxychromone isolated from DME is one of the active compounds that may contribute to regulate blood glucose levels.

Growth, serum biochemistry, complement activity, and liver gene expression responses of Pekin ducklings to graded levels of cultured aflatoxin B1

A 14-d study was conducted to evaluate the effects of cultured aflatoxin B1 (AFB1) on performance, serum biochemistry, serum natural antibody and complement activity, and hepatic gene expression parameters in Pekin ducklings. A total of 144 male Pekin ducklings were weighed, tagged, and randomly allotted to 4 dietary treatments containing 4 concentrations of AFB1 (0, 0.11, 0.14, and 0.21 mg/kg) from 0 to 14 d of age (6 cages per diet; 6 ducklings per cage). Compared with the control group, there was a 10.9, 31.7, and 47.4% (P < 0.05) decrease in cumulative BW gain with 0.11, 0.14, and 0.21 mg of AFB1/kg of diet, respectively, but feed efficiency was not affected. Increasing concentrations of AFB1 reduced cumulative BW gain and feed intake both linearly and quadratically, and regression equations were developed with r2 ≥0.73. Feeding 0.11 to 0.21 mg of AFB1/kg reduced serum glucose, creatinine, albumin, total protein, globulin, Ca, P, and creatine phosphokinase linearly, whereas serum urea N, Cl, alkaline phosphatase, and aspartate amino transferase concentrations increased linearly with increasing AFB1 (P < 0.05). Additionally, 0.11 to 0.21 mg of AFB1/kg diets impaired classical and alternative complement pathways in the duckling serum when tested by lysis of rabbit, human type O, and horse erythrocytes, and decreased rabbit and horse agglutinins (P < 0.05). Liver peroxisome proliferator activated receptor α (PPARα) expression was linearly downregulated by AFB1 (P < 0.01). Results from this study indicate that for every 0.10 mg/kg increase in dietary AFB1, cumulative feed intake and BW gain decrease approximately 230 and 169 g per duckling from hatch to 14 d; and that AFB1 at very low concentrations can significantly impair liver function and gene expression, and innate immune dynamics in Pekin ducklings.

Effect of chronic administration of hexane extract of Byrsonima crassifolia seed on B-cell and pancreatic oxidative parameters in streptozotocin-induced diabetic rat.

In Mexican traditional medicine, the seeds of Byrsonima crassifolia have been used in the treatment of diabetes, rheumatism and for wound healing. The aim was to evaluate the effect of seeds of B. crassifolia on insulin release from the pancreatic beta cells in streptozotocininduced diabetic rats. In the present study, we evaluated the beneficial effect of seeds B. crassifolia streptozotocin-induced type 1 diabetic rats. Insulin level; insulin sensitivity index, insulin content in pancreas, malonaldehyde, nitric oxide contents, oxidative stress parameters were assayed. Serum glucose levels were determined by the glucose oxidase method. To determine the insulin releasing activity, after extract treatment, the pancreas was excised. Pancreatic sections were processed for examination of insulin-releasing activity using an imunocytochemistry kit. Administration of the hexane extract (200 and 400 mg/kg), exhibited a significant reduction in serum glucose. Administration of streptozotocin decreased the number of beta cells with insulin secretory activity in comparison with intact rats; but treatment with the B. crassifolia seed extract increased significantly the activity of the beta cells in comparison with the diabetic control rats. The extract decreased serum glucose in streptozotocin-induced diabetic rats and increased insulin release from the beta cells of the pancreas. These finding suggest that B. crassifolia seed has beneficial effect for diabetes through decreasing blood glucose and lipid levels, increasing insulin sensitivity index and insulin content, up-regulating antioxidant enzyme activity and decreasing lipid peroxidation.

The protective effect of N-acetylcysteine on oxidative stress in the brain caused by the long-term intake of aspartame by rats.

Long-term intake of aspartame at the acceptable daily dose causes oxidative stress in rodent brain mainly due to the dysregulation of glutathione (GSH) homeostasis. N-Acetylcysteine provides the cysteine that is required for the production of GSH, being effective in treating disorders associated with oxidative stress. We investigated the effects of N-acetylcysteine treatment (150 mg kg(-1), i.p.) on oxidative stress biomarkers in rat brain after chronic aspartame administration by gavage (40 mg kg(-1)). N-Acetylcysteine led to a reduction in the thiobarbituric acid reactive substances, lipid hydroperoxides, and carbonyl protein levels, which were increased due to aspartame administration. N-Acetylcysteine also resulted in an elevation of superoxide dismutase, glutathione peroxidase, glutathione reductase activities, as well as non-protein thiols, and total reactive antioxidant potential levels, which were decreased after aspartame exposure. However, N-acetylcysteine was unable to reduce serum glucose levels, which were increased as a result of aspartame administration. Furthermore, catalase and glutathione S-transferase, whose activities were reduced due to aspartame treatment, remained decreased even after N-acetylcysteine exposure. In conclusion, N-acetylcysteine treatment may exert a protective effect against the oxidative damage in the brain, which was caused by the long-term consumption of the acceptable daily dose of aspartame by rats.

Rejuvenating of Kidney Tissues on Alloxan Induced Diabetic Mice under the Effect ofMomordica charantia

Diabetes mellitus is a chronic disorder in human and responsible for different complications and also causes mortality and morbidity. A wide number of herbal products are employed in the treatment of diabetes for their better efficacy and safety compared to synthetic medicine. The present studies have established the antidiabetic potential and rejuvenating capacity of kidney tissues under the effect of extract. Diabetes was induced in the Swiss albino mice by injecting alloxan at the dose of 150 mg/kg body weight and aqueous extract ofMomordica charantiafruits at doses of 100 mg/kg body weight and 250 mg/kg body weight was administered orally for three weeks. After 21 days of treatment of the aqueous extracts ofMomordica charantiasignificantly reduces serum glucose level, kidney function tests, lipid peroxidation as well as histopathological study also did show adverse alternation in the morphological architecture of the kidney tissue. Thus, from this study we concluded thatMomordica charantiaexhibited significant antihyperglycemic and rejuvenating capacity of kidney tissues activities in alloxan induced diabetic mice.

Chronic unpredictable stress regulates visceral adipocyte-mediated glucose metabolism and inflammatory circuits in male rats

Chronic psychological stress is a prominent risk factor involved in the pathogenesis of many complex diseases, including major depression, obesity, and type II diabetes. Visceral adipose tissue is a key endocrine organ involved in the regulation of insulin action and an important component in the development of insulin resistance. Here, we examined for the first time the changes on visceral adipose tissue physiology and on adipocyte‐associated insulin sensitivity and function after chronic unpredictable stress in rats. Male rats were subjected to chronic unpredictable stress for 35 days. Total body and visceral fat was measured. Cytokines and activated intracellular kinase levels were determined using high‐throughput multiplex assays. Adipocyte function was assessed via tritiated glucose uptake assay. Stressed rats showed no weight gain, and their fat/lean mass ratio increased dramatically compared to control animals. Stressed rats had significantly higher mesenteric fat content and epididymal fat pad weight and demonstrated reduced serum glucose clearing capacity following glucose challenge. Alterations in fat depot size were mainly due to changes in adipocyte numbers and not size. High‐throughput molecular screening in adipocytes isolated from stressed rats revealed activation of intracellular inflammatory, glucose metabolism, and MAPK networks compared to controls, as well as significantly reduced glucose uptake capacity in response to insulin stimulation. Our study identifies the adipocyte as a key regulator of the effects of chronic stress on insulin resistance, and glucose metabolism, with important ramifications in the pathophysiology of several stress‐related disease states.

Pank1 deletion in leptin-deficient mice reduces hyperglycaemia and hyperinsulinaemia and modifies global metabolism without affecting insulin resistance.

Pantothenate kinase (PANK) is the first enzyme in CoA biosynthesis. Pank1-deficient mice have 40% lower liver CoA and fasting hypoglycaemia, which results from reduced gluconeogenesis. Single-nucleotide polymorphisms in the human PANK1 gene are associated with insulin levels, suggesting a link between CoA and insulin homeostasis. We determined whether Pank1 deficiency (1) modified insulin levels, (2) ameliorated hyperglycaemia and hyperinsulinaemia, and (3) improved acute glucose and insulin tolerance of leptin (Lep)-deficient mice. Serum insulin and responses to glucose and insulin tolerance tests were determined in Pank1-deficient mice. Levels of CoA and regulating enzymes were measured in liver and skeletal muscle of Lep-deficient mice. Double Pank1/Lep-deficient mice were analysed for the diabetes-related phenotype and global metabolism. Pank1-deficient mice had lower serum insulin and improved glucose tolerance and insulin sensitivity compared with wild-type mice. Hepatic and muscle CoA was abnormally high in Lep-deficient mice. Pank1 deletion reduced hepatic CoA but not muscle CoA, reduced serum glucose and insulin, but did not normalise body weight or improve acute glucose tolerance or protein kinase B phosphorylation in Lep-deficient animals. Pank1/Lep double-deficient mice exhibited reduced whole-body metabolism of fatty acids and amino acids and had a greater reliance on carbohydrate use for energy production. The results indicate that Pank1 deficiency drives a whole-body metabolic adaptation that improves aspects of the diabetic phenotype and uncouples hyperglycaemia and hyperinsulinaemia from obesity in leptin-deficient mice.

Berberis Fruit Extract and Biochemical Parameters in Patients With Type II Diabetes.

Diabetes mellitus is a common medical problem. There is in fact a growing body of literature on plants used for the treatment of diabetes. Plant materials attracted considerable interest of scientists. In this respect, in the past few years, attempts were made to use natural plant products for the treatment of patients with diabetes. The aim of this study was to investigate the effect of Berberis fruit extract to achieve glycemic control in patients with Type II diabetes. This study was performed between July 2010 and April 2013. Thirty patients of type II diabetes admitted to Ayatollah Rohhani hospital were recruited. Patients' sera were collected for the assessment of glucose and HbA1c values. Biochemical analyses were performed before and after treatment by Berberis fruit extract. Biochemical parameters were measured by spectrophotometric method (Jenway uv/vis, 6505 model, Dunmow, UK). Glucose level was measured by glucose oxidase method kit (Pars Azmoon, Tehran, IR Iran). Serum total cholesterol and triglycerides were measured using standard biochemical kits (Pars Azmoon, Tehran, Iran). Blood glycated hemoglobin level was measured by using Elisa kit (Bioassay technology laboratory, Elisa kit). Experiments were performed in triplicate in at least three separate experiments. Our findings demonstrated that patients with type 2 diabetes who received barberry fruit had significant reduction in serum glucose to 136.15 ± 32.8 mg/dL and decreased HbA1c levels to 7.07 ± 1.21 mg/dL, during the 8 weeks of study. This investigation revealed that Berberis fruit extract has beneficial metabolic effects in patients with type II diabetes. Barberry may improve glucose catabolism via glycolysis pathway, stimulate insulin secretion or improve insulin function and finally decrease glucose uptake. Our results indicated that Berberis fruit regulates glucose metabolism in patients with type 2 diabetes.

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.