Lipid Metabolism In Diabetic Rats Research Articles

Resveratrol Regulates Glucose and Lipid Metabolism in Diabetic Rats by Inhibition of PDK1/AKT Phosphorylation and HIF-1α Expression.

To explore the underlying mechanism of the anti-diabetic effect of resveratrol (RSV) on regulating glycolipid metabolism in diabetic rats induced by streptozotocin (STZ) and a high-fat diet (HFD). Male Wistar rats were randomized into three groups. Two groups were fed a high-fat diet and intraperitoneally injected with STZ (35 mg/kg), with one group also treated with RSV (30 mg/kg/d), and the third, control group was fed a normal diet. After 12 weeks, blood lipid levels and fasting blood glucose (FBG) were assessed. Histopathological changes were evaluated by hematoxylin-eosin (HE) staining and periodic acid-Schiff (PAS) staining. The protein expression of hypoxia-inducible factor 1α (HIF-1α) was assessed by Western blotting and immunofluorescence, and the proteins level of 3-phosphoinositide-dependent protein kinase 1 (PDK1), phosphorylated-PDK1 (p-PDK1), phosphorylated-protein kinase B (p-AKT), glucose transporter 1 (GLUT1) and low-density lipoprotein receptor (LDLR) in the liver were analyzed by Western blotting. The mRNA levels of Hif-1α, Glut1 and Ldlr in the liver were determined by RT-qPCR. RSV treatment significantly reduced liver/body weight ratio (L/W, P < 0.05), FBG (P < 0.01) and serum concentrations of total cholesterol (TC, P < 0.05), triglycerides (TG, P < 0.01) and low-density lipoprotein-cholesterol (LDL-C, P < 0.05) in diabetic rats. RSV also improved diabetic symptoms, attenuated liver steatosis and increased liver glycogen accumulation. RSV treatment significantly downregulated the proteins expression of p-PDK1 and p-AKT (P < 0.01) and the levels of HIF-1α (P < 0.05) and GLUT1 (P < 0.01), while significantly upregulating the level of LDLR (P < 0.05). RSV was effective in improving glycolipid metabolism in diabetic rats, probably by inhibiting the PDK1/AKT/HIF-1α pathway and regulation of its downstream target levels. These findings may provide new insight into the mechanism of action of RSV in the treatment of diabetes.

Influence of Dietary Chitosan Feeding Duration on Glucose and Lipid Metabolism in a Diabetic Rat Model.

This study was designed to investigate the influence of dietary chitosan feeding-duration on glucose and lipid metabolism in diabetic rats induced by streptozotocin and nicotinamide [a non-insulin-dependent diabetes mellitus (NIDDM) model]. Male Sprague-Dawley rats were used as experimental animals and divided into short-term (6 weeks) and long-term (11 weeks) feeding durations, and each duration contained five groups: (1) control, (2) control + 5% chitosan, (3) diabetes, (4) diabetes + 0.8 mg/kg rosiglitazone (a positive control), and (5) diabetes + 5% chitosan. Whether the chitosan feeding was for 6 or 11 weeks, the chitosan supplementation decreased blood glucose and lipids levels and liver lipid accumulation. However, chitosan supplementation decreased plasma tumor necrosis factor (TNF)-α, insulin levels, alanine aminotransferase (ALT) activity, insulin resistance (HOMA-IR), and adipose tissue lipoprotein lipase activity. Meanwhile, it increased plasma high-density lipoproteins (HDL)-cholesterol level, plasma angiopoietin-like-4 protein expression, and plasma triglyceride levels (at 11-week feeding duration only). Taken together, 11-week (long-term) chitosan feeding may help to ameliorate the glucose and lipid metabolism in a NIDDM diabetic rat model.

Licochalcone E improves insulin sensitivity in palmitic acid-treated HepG2 cells through inhibition of the NLRP3 signaling pathway

Our previous research demonstrated that compound licochalcone E can reduce glucose tolerance and lipid metabolism in diabetic rats, although its mechanism remains unknown. Here, we used palmitic acid (PA) to establish a PA-treated HepG2 model, and then examined glucose uptake, glucose consumption, and blood lipids to evaluate the effects of licochalcone E within the safe dose range in the model. Polymerase chain reaction (PCR) was used to detect the expression levels of key genes associated with liver gluconeogenesis; enzyme-linked immunosorbent assay (ELISA) was deployed to evaluate the concentration of inflammatory factors; and laser confocal microscopy and western blot were used to determine the levels of reactive oxygen species (ROS) and NLRP3 inflammasome signaling pathway-related proteins, respectively. Finally, molecular simulations were exploited to validate the interaction between licochalcone E and the NLRP3 inflammasome. The results demonstrated that licochalcone E showed no toxicity in the dose range of 2.5–40 μM. In this dose range, licochalcone E substantially increased the uptake and consumption of glucose in the insulin resistance model and dose-dependently reduced the concentration of total cholesterol. The PCR results indicated that licochalcone E dose-dependently reduced the expression of Glucose-6-phosphatase (G6Pase) and Phosphoenolpyruvate carboxykinase (PEPCK) genes and increased the expression of Glucose Transporter 4 (Glut4) in PA-treated HepG2. Moreover, the ELISA results revealed that licochalcone E significantly reduced the expression of TNF-α, IL-1β, and IL-18. Confocal microscopy results showed that licochalcone E dramatically reduced the generation of ROS and the expressions of NLRP3 and its downstream caspase-1 in PA-treated HepG2 model. Western blot results further indicated that licochalcone E significantly reduced the expression of NLRP3, caspase-1 and IL-1β in the model. Additionally, molecular simulations demonstrated that licochalcone E has good binding affinity for the NLPR3 inflammasome. We concluded that licochalcone E has the potential to be used as an insulin sensitizer by reducing the release of ROS and inflammatory factors following inhibition of the NLPR3 signaling pathway.

Improvement of Postprandial Lipid Metabolism After Ileal Transposition in Non-obese Diabetic Rats.

Ileal transposition (IT) could reduce obesity and improve type 2 diabetes mellitus (T2DM). The main aim of our study was to investigate lipid metabolism changes in T2DM rats after IT without a weight reduction effect. Thirty male diabetic rats were randomly divided into IT, sham IT (SI), and control groups. The levels of plasma cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs), and bile acid were measured. After sacrifice, the white adipose tissue, brown adipose tissue and liver were weighed. IT induced significant improvement in glucose and lipid metabolism. There were no significant differences in the levels of cholesterol (P = 0.87), HDL (P = 0.70), LDL (P = 0.96), or TGs (P = 0.97) among the groups before surgery. After IT, the levels of cholesterol (P = 0.019), LDL (P = 0.004), and TGs (P < 0.001) were lower than those in the SI and control groups, while the level of HDL was not significantly different compared to those of the other groups (P = 0.437). Higher bile acid level (P = 0.001), lower white adipose tissue/total body weight ratio (P < 0.001), and lower liver/total body weight ratio (P = 0.003) were found in the IT group. The BAT/total body weight ratio in the IT group was higher than that in the SI or control groups (P = 0.002). IT could improve lipid metabolism in diabetic rats.

The role of estrogen-related receptor α (ERRα) in metabolic adaptations by endurance training in skeletal muscle of streptozotocin-induced diabetic rats

The aim of present study was to investigate the effect of endurance training and ERRα inhibition (target for the discovery of new therapies for diseases such as diabetes) on the gene and protein expression of factors involved in lipid metabolism in diabetic rats. We designed the current study to evaluate the combination of ERRα inhibition and exercise training effects on the expression of ERRα, medium-chain acyl-CoA dehydrogenase (MCAD), carnitine palmitoyltransferase-1b (CPT-1b), pyruvate dehydrogenase kinase 4 (PDK4) and Citrate synthase (CS) in diabetic and non-diabetic rats. Sixty-four male Wistar rats were divided into 8 groups (n = 8) as follows: non-diabetic control, diabetic control (a single dose of 45 mg/kg of STZ), non-diabetic/ERRα inhibition group (received 0.48 mg/kg of XCT790), diabetic/ERRα inhibition group, non-diabetic/exercise training, diabetic/exercise training, non-diabetic rats which received XCT790 and performed exercise training, and diabetic rats which received XCT790 and also performed exercise training. The gene and protein expression were measured by real-time PCR (quantified by $$ 2^{{ - \Delta \Delta CT }}$$ method) and Western blotting method, respectively. Our results showed that the expression of ERRα (1.6-fold), MCAD (4.6-fold), CPT-1b (fivefold), CS (twofold), PDK4 (fourfold), and PGC-1α (fourfold) in the medial gastrocnemius muscle of the non-diabetic exercise training group was significantly higher than the non-diabetic control group. In sum, ERRα is a trainable factor, and its changes are parallel with higher expression of the enzymes which involved in lipid metabolism in healthy rats. ERRα inhibition and endurance training may have positive effects on the lipid metabolism in diabetic rats. This indirectly suggests a significant role of ERRα in the adaptation of lipid metabolism evoked by endurance training.

Evaluation of anti-diabetic activity of Trianthema portulacastrum Linn in Dithizone induced diabetes in Wistar rats

Trianthema portulacastrum Linn. Whole plant is an extensively used plant for medication in India for the treatment of various health issues. This study was focused to prefigure the antidiabetic potency of Chloroform extract of the Trianthema portulacastrum (CETP) whole plant administered at two doses (100mg/kg and 200 mg/kg) for the duration of 21days in Dithizone - induced diabetic rats. The rats were separated into five groups, each group containing six animals. All Groups except Group I were made diabetic by intraperitonial administration of Dithizone(50mg/kg). Group I served as control group, Group II served as diabetic control received Dithizone(50mg/kg), Group III rats were administered with glibenclamide (10mg/kg), a standard oral hypoglycemic agent while Group IV and Group V diabetic rats were served with 100 mg/kg and 200 mg/kg of CETP whole plant respectively. Potency of the plant extract as an antidiabetic was assessed in dithizone induced diabetic models by comparing biochemical parameters like blood glucose level, Glucose tolerance, lipid profiles along with the liver antioxidant enzymes, glycogen content and Glycogenic enzymes which were quantified using standard experimental procedures. There exists a significant reduction in levels of blood glucose, raise in glucose tolerance, and improved imbalance in lipid metabolism in diabetic rats after administration of the extract at 100mg/kg and 200mg/kg. T.portulacastrum with 200mg/kg of the extract showed the best hypoglycemic action by comparing favorably well with Glibenclamide. This investigation clearly showed that, the extract is endowed with hypoglycemic activity, T.portulacastrum may also defend the deterioration of liver due to diabetes.

Effect of Aglycon and Glycoside Flavonoid-Enriched Extracts Obtained from Buxus sempervirens L. on Glucose and Lipid Metabolism in Diabetic Rats.

Buxus sempervirens L. is a medicinal plant with several beneficial effects on health and is widely used in Moroccan folklore as an antidiabetic plant. The aim of this study was to evaluate the antidiabetic effect of both aglycone and glycoside flavonoid enriched extracts of this plant in the experimental diabetic state. In the current work, the effect of aglycone and glycoside flavonoid-enriched extracts from the leaves of Buxus sempervirens L. (AFBS and GFBS) (10 mg/kg) on blood glucose levels has been evaluated in normal and streptozotocin (STZ) diabetic rats. Moreover, the histopathological changes in the liver and pancreas have been assessed in STZ diabetic rats. The ability of AFBS and GFBS to improve glucose tolerance in normal rats was also evaluated. In normal rats, both a single and repeated administration of AFBS and GFBS (10 mg/kg) showed no significant effects on blood glucose levels. However, both single and repeated oral administration of the two fractions showed a significant blood glucose lowering effect (p<0.0001) in STZ rats. In addition, histopathological analysis has demonstrated the beneficial impact of AFBS and GFBS on the pancreas and liver. Whereas, the oral glucose tolerance test demonstrated no significant ability of these extracts to improve the increase in blood glucose levels in normal and diabetic treated rats. In the current study, no significant changes in body weight in normal and STZ rats have been shown. In addition, the antioxidant activity of both AFBS and GFBS revealed the antioxidant effect of both extracts. Furthermore, both flavonoid-enriched fractions had no significant effect on blood lipid levels. In conclusion, AFBS and GFBS exhibited an interesting antidiabetic effect on streptozotocin rats and GFBS which seems to be more effective than AFBS.

Expression of high mobility group protein B1 in periodontal tissues and its association with hepatic lipid metabolism in diabetic rats with periodontitis

To investigate the expression of high mobility group box-1 protein (HMGB1) and its downstream products, receptor for advanced glycation end-products (RAGE) and tumor necrosis factor-α (TNF-α), in periodontal tissues of diabetic rats with periodontitis, and explore the association of HMGB1 with hepatic lipid metabolism. Immunohistochemical staining was used to detect the expression of HMGB1, RAGE and TNF-α in the periodontal tissues in rat models of diabetes mellitus (DM), periodontitis (CP), and diabetic periodontitis (DM + CP). The serum levels of the indicators of lipid metabolism and biochemical indexes of liver damage were detected by spectroscopy. The expressions of HMGB1 and RAGE in the periodontal tissues were significantly higher in DM group than in the control group, but the expression of TNF-α showed no significant difference among the groups. In CP group, the expressions of HMGB1 and TNF-α were significantly higher than those in the control group, and the expression of RAGE was comparable with that in the control group but significantly lower than that in DM and DM+CP group. The expressions of HMGB1, RAGE and TNF-α were all significantly higher in DM+CP group than in the control group. Compared with the control rats, the rats in DM, CP, DM+CP group all showed abnormal hepatic lipid metabolism with significantly elevated serum ALT levels. HMGB1 and RAGE participate in the inflammation of the periodontal tissues in diabetic rats. Diabetes leads to elevated expression of HMGB1 in the periodontal tissues. Both periodontitis and hyperglycemia contribute to liver metabolic dysfunction. HMGB1- RAGE provides clues in the study of signaling pathways underlying the mutual susceptibility of diabetes and periodontitis.

Improved FGF21 Sensitivity and Restored FGF21 Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats After Duodenal-Jejunal Bypass and Sleeve Gastrectomy.

Objective: Bariatric surgery can profoundly improve glucose and lipid metabolism in diabetic rats. Fibroblast growth factor 21 (FGF21) is an important hormone with multiple metabolic beneficial effects. Alteration in serum FGF21 level after bariatric surgery has been reported with conflicting results. Here, we investigated the effect of bariatric surgeries on FGF21 expression and sensitivity.Methods: We performed duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG) and sham surgery in diabetic rats induced by high fat diet and streptozotocin. Metabolic parameters, including body weight, food intake, glucose tolerance, and lipid profiles, were monitored. FGF21 levels in both serum and liver were measured after surgery. FGF21 signaling pathway including FGF receptor 1 (FGFR1), β-klotho (KLB), and phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) was detected in the liver and white adipose tissue (WAT). We also determined FGF21 sensitivity post-operatively by acute recombinant human FGF21 injection. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted immediately after FGF21 injection. Serum triglyceride (TG) and non-esterified fatty acid (NEFA) were measured and the mRNA levels of early growth response 1 (Egr1) and c-Fos in the liver and WAT were detected after FGF21 injection.Results: Improvements in glucose tolerance, insulin sensitivity, and lipid profiles were observed after bariatric surgeries along with ameliorated lipid metabolism in the liver and WAT. Serum and hepatic FGF21 levels decreased in both DJB and SG groups. FGFR1 and phosphorylated ERK1/2 levels increased in both DJB and SG groups 8 weeks after surgery. The expression of KLB was downregulated only in the WAT after DJB and SG. Significant alteration of OGTT and ITT were observed after acute FGF21 administration in DJB and SG groups. Serum TG and NEFA in DJB and SG groups also decreased after FGF21 administration. And increased mRNA levels of Egr1 and c-Fos were detected in the liver and WAT after DJB and SG surgeries.Conclusions: DJB and SG surgeries can downregulate hepatic expression of FGF21, restore FGF21 signaling pathway and improve FGF21 sensitivity in high-fat diet/streptozotocin-induced diabetic rats.

Regulation of lipid metabolism in diabetic rats by Arctium lappa L. polysaccharide through the PKC/NF-κB pathway

Diabetic patients often have lipid metabolism disorders, which can lead to life-threatening complications. In this study, we investigated the regulatory effects of polysaccharides extracted from Arctium lappa L. on lipid metabolism in diabetic rats. We constructed a diabetes mellitus mouse model with streptozocin, and treated the rats with A. lappa L. polysaccharide. The body weight analysis showed that the weight of diabetic rats significantly decreased, but the weight of the rats in the polysaccharide treatment groups increased and the ratio of liver weight to body weight also appeared the well effect (tending to normal group). Serum biochemical analysis showed that total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL), and the ratio of liver weight to body weight showed a downward trend. In addition, compared to TC/HDL, TG/HDL, and HDL/LDL, the relative content of HDL was increased. Meanwhile, we used Western blotting to detect changes in protein kinase C alpha (PKC-α), PKC-β, P-selectin, nuclear factor kappa B (NF-κB), and phosphorylated NF-kB p65 in the liver. The results showed that the A. lappa L. polysaccharides regulated lipid metabolism through the PKC/NF-κB pathway in diabetic rats.

Polyphenol-enriched extract of Rosa rugosa Thunb regulates lipid metabolism in diabetic rats by activation of AMPK pathway

This study was designed to investigate the mechanism of polyphenol-enriched extract of Rosa rugosa Thunb (RPE) in the control of dyslipidemia in diabetic rats. RPE was tested at three dosages (37.5 mg/kg, 75 mg/kg and 150 mg/kg) in the rat dyslipidemia model established with high fat diet feeding in combination with STZ injection (30 mg/kg). The RPE effect was evaluated after 4 weeks of treatment. In the RPE-treated rats, hepatic total cholesterol (TC) and triglyceride (TG) were significantly reduced, lipoprotein lipase (LPL) and liver lipase (HL) were significantly increased. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were decreased in the serum. Those effects of RPE were observed primarily at the mediate and high dosages. Expression of FGF21 was increased in the liver tissue and hepatic cell line 1c1c7 by RPE. The signals of p-AMPK, p-ACC, ACC, p-SIRT, and PGC-1α were significantly induced in the liver by RPE. The results suggest that RPE may improve hepatic steatosis and liver function by induction of AMPK signaling activity in the control of dyslipidemia.

Effect of Aqueous Extract of Phaseolus Vulgaris on the Regulation of Glucose and Lipid Metabolism in Diabetic Rats

Effect of Aqueous Extract of Phaseolus Vulgaris on the Regulation of Glucose and Lipid Metabolism in Diabetic Rats

Chronic intermittent hypobaric hypoxia ameliorates diabetic nephropathy through enhancing HIF1 signaling in rats

AimOur previous study demonstrated that chronic intermittent hypobaric hypoxia (CIHH) had anti-diabetes effect. The present study was to explore the renal protective effect of CIHH in diabetic rats. MethodsSprague–Dawley rats were randomly divided into three groups: diabetes mellitus group (DM, induced by high-fat diet combined with low-dose streptozotocin), diabetes plus CIHH treatment group (DM+CIHH, simulated 5000-m altitude, 6h per day for 28days, after diabetes model confirmed) and control group (CON). Systolic arterial blood pressure (SAP), blood biochemicals, urinary albumin, and histopathology of kidney were determined. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) level, protein levels of hypoxia induced factors (HIFs) and transforming growth factor β1 (TGF-β1) in kidney were assayed. ResultsThe increased SAP, urinary albumin, hyperplasia of glomerular, fibrosis in mesangial and glomerular, and abnormal lipid metabolism in diabetic rats were ameliorated by CIHH treatment. And decreased superoxide dismutase (SOD) activity and increased malondialdehyde (MDA) level in diabetic kidney were reversed in CIHH-treated DM rats. In addition up-regulated TGF-β1 and down-regulated HIF1α in diabetic kidney returned back to normal level in CIHH-treated DM rats. ConclusionsThese data demonstrated for the first time that CIHH had protective effects against the early stage damage of diabetic nephropathy through activating HIF1 signaling, improving anti-oxidation and inhibiting TGF-β1 signaling in diabetic rats.

Anti-diabetic effects of soluble and insoluble dietary fibre from deoiled cumin in low-dose streptozotocin and high glucose-fat diet-induced type 2 diabetic rats

The effects of soluble dietary fibre (SDF) and insoluble dietary fibre (IDF) from deoiled cumin on low-dose streptozotocin and high glucose-fat-induced type 2 diabetes rats were examined. Male Wistar rats were divided into nine groups: control (non-diabetic, no SDF or IDF intake), model (diabetes only), metformin, high-dose SDF (5 g/kg body weight), middle-dose SDF (500 mg/kg body weight), low-dose SDF (250 mg/kg body weight), high-dose IDF (5 g/kg body weight), middle-dose IDF (500 mg/kg body weight), and low-dose IDF (250 mg/kg body weight). SDF treatments, in particular, middle-dose SDF for 4 weeks, induced better regulation of blood glucose, insulin, hormones, and liver lipid metabolism in diabetic rats, accompanied by increased levels of short-chain fatty acids in colon and decreased fatty degeneration of liver. Our results collectively support the therapeutic potential of SDF from deoiled cumin in type 2 diabetes.

Comparative anti-inflammatory and lipid-normalizing effects of metformin and omega-3 fatty acids through modulation of transcription factors in diabetic rats.

BackgroundEmerging evidence suggests beneficial effects of omega-3 fatty acids on diabetic complications. The present study compared the progressive effects of metformin and flax/fish oil on lipid metabolism, inflammatory markers, and liver and renal function test markers in streptozotocin-nicotinamide-induced diabetic rats.MethodsStreptozotocin-induced diabetic rats were randomized into control and four diabetic groups: streptozotocin (STZ), metformin (200 mg/kg body weight (b.w)/day (D)), flax and fish oil (500 mg/kg b.w/D).ResultsMetformin and flax and fish oil exhibited increased expression of transcription factor peroxisome proliferator-activated receptor γ while the treatment downregulated sterol regulatory element-binding protein 1 and nuclear factor kβ as compared to those of the STZ group. Apart from modulation of transcription factor expression, the expression of fatty acid synthase, long chain acyl CoA synthase, and malonyl-CoA-acyl carrier protein transacylase was lowered by flax/fish oil treatment. Serum cholesterol, triglycerides, and VLDL were also significantly reduced in the treatment groups as compared to those in the STZ group. Although pathological abnormalities were seen in the liver and kidneys of rats on metformin, no significant changes in liver/renal function markers were observed at day 15 and day 30 of the treatment groups. Flax/fish oil had protective effects toward pathological abnormalities in the liver and kidney. Flax/fish oil improved lipid profile and alkaline phosphatase at day 30 as compared to that at day 15.ConclusionsThe present study demonstrates potential beneficial effects of metformin and flax/fish oil intervention in improving serum lipid profile by regulating the expression of transcription factors and genes involved in lipid metabolism in diabetic rats. In addition, these interventions also lowered the expression of atherogenic cytokines. The protective effects of flax/fish oil are worth investigating in human subjects on metformin monotherapy.

Effect of hypothalamic-pituitary-adrenal axis alterations on glucose and lipid metabolism in diabetic rats.

This study investigated the relationship between alterations in the hypothalamic-pituitary-adrenal (HPA) axis function and glucose and lipid metabolism in diabetic rats. To accomplish this a diabetes model was established by jointly administering a long-term high-fat diet plus Streptozotocin (STZ; 50 mg/kg ip). The rats were randomly divided into four groups: 1) a normal control group, 2) a model group, 3) astragalus polysaccharide (APS) group, and 4) a metformin group. APS and metformin hydrochloride were administered intragastrically (100 mg∙kg(-1)d(-1)). Rat blood glucose and body weight were measured once per week, and urine was collected for 24 h after 30 days of administration of APS. The levels of blood lipids, insulin, and corticosterone (CORT), as well as hypothalamic CRH, pituitary ACTH, urine sugar and CORT were measured. Compared with the normal control group, the levels of blood sugar, urine sugar, TC, and TG significantly increased in the model group, and the levels of hepatic glycogen and HDL-C decreased. Administration of APS was shown to reverse these changes. Furthermore, as compared with the normal control group, the levels of insulin and hypothalamic CRH in the model group decreased significantly, while the levels of plasma ACTH and CORT, pituitary ACTH, and urine CORT were elevated. Again, APS administration improves these outcomes and returns their levels to normal. Thus, the glucose and lipid metabolic disorder in the high-fat diet and STZ-induced diabetes model may be related to increased HPA axis activity. The hypoglycemic effect of the traditional Chinese medicine, ASP, may improve HPA axis functioning and aid in the treatment of diabetes.

Amorphous solid dispersion of berberine with absorption enhancer demonstrates a remarkable hypoglycemic effect via improving its bioavailability

Low oral bioavailability of berberine due to poor solubility and membrane permeability limits its clinical use for treatment of diabetes. We developed an amorphous solid dispersion of berberine with absorption enhancer sodium caprate, referred to as Huang-Gui Solid Dispersion (HGSD) preparations, and examined them for improvement of dissolution and oral bioavailability. HGSDs were prepared by solvent evaporation, and the formulations of amorphous solid dispersions were characterized by X-ray diffraction, differential scanning calorimetry and scanning electron microscopy. According to in vitro solubility and dissolution studies, P9, the 9th production of HGSDs based on orthogonal test, was sorted out. Then pharmacokinetic behavior of P9 was evaluated by in vitro membrane permeation, in situ intestinal perfusion, and in vivo bioavailability in rats. Furthermore, the anti-diabetic effect of P9 was examined in a type 2 diabetic rat model. It was found that majority of berberine in P9 existed in an amorphous form, and its solubility and dissolution rate were significantly increased. Pharmacokinetic studies demonstrated a 3-fold increase in in vitro membrane permeation, a 4-fold increase in in situ intestinal perfusion and a 5-fold increase in vivo bioavailability of P9 compared to berberine or berberine tablets. In addition, oral administration of P9 (100mg/kg) improved glucose and lipid metabolism in diabetic rats compared to pure berberine (100mg/kg), berberine tablets (100mg/kg) or metformin (300 mg/kg) treatment. These findings indicate that P9 enhances oral bioavailability of berberine and may be a potential candidate drug for treatment of diabetes.

Antihyperlipidemic effects of mature coconut water and its role in regulating lipid metabolism in alloxan-induced experimental diabetes

The present study aims to evaluate the antihyperipidemic effects of mature coconut water (MCW), a natural nutritious beverage and its role in regulating lipid metabolism in experimental diabetes. The experimental animals were divided into four groups—normal control, MCW-alone-treated rats, diabetic control, and diabetic rats treated with MCW. Blood glucose, lipid profile, atherogenic index, phospholipids in various tissues, free fatty acids, activities of various lipogenic enzymes, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase in liver, lecithin–cholesterol acyl transferase (LACT) in plasma, and lipoprotein lipase (LPL) in heart were evaluated in all the experimental groups. The results indicate that in diabetic rats, MCW treatment reduced the blood glucose and lipid levels in blood and other tissues along with reduced activity of HMG CoA reductase and increased activity of LACT and LPL. In addition, levels of triglycerides, phospholipids, and free fatty acids in various tissues and atherogenic index were significantly lowered. In conclusion, MCW significantly reduced hyperlipidemia and regulated the defects in lipid metabolism in diabetic rats, indicating the therapeutic potential of MCW in diabetes and associated atherogenic complications.

Evaluation of Antidiabetic Activity and Associated Toxicity ofArtemisia afraAqueous Extract in Wistar Rats

Artemisia afra Jacq. ex Willd. is a widely used medicinal plant in South Africa for the treatment of diabetes. This study aimed to evaluate the hypoglycemic activity and possible toxicity effect of aqueous leaf extract of the herb administered at different dosages for 15 days in streptozotocin-induced diabetic rats. Administration of the extract at 50, 100, and 200 mg/kg body weight significantly (P < 0.05) increased body weight, decreased blood glucose levels, increased glucose tolerance, and improved imbalance in lipid metabolism in diabetic rats. These are indications of antidiabetic property of A. afra with 200 mg/kg body weight of the extract showing the best hypoglycemic action by comparing favourably well with glibenclamide, a standard hypoglycemic drug. The extract at all dosages tested also restored liver function indices and haematological parameters to normal control levels in the diabetic rats, whereas the kidney function indices were only normalized in the diabetic animals administered with 50 mg/kg body weight of the extract. This investigation clearly showed that in addition to its hypoglycemic activity, A. afra may also protect the liver and blood against impairment due to diabetes. However, some kidney functions may be compromised at high dosages of the extract.

Possible mechanism of the cardio-renal protective effects of AVE-0991, a non-peptide Mas-receptor agonist, in diabetic rats

This study was designed to investigate the cardio-renal protective effect of AVE-0991, a non-peptide Mas-receptor agonist, and A-779, a Mas-receptor antagonist, in diabetic rats. Wistar rats treated with streptozotocin (50 mg/kg, i.p., once), developed diabetes mellitus after 1 week. After 8 weeks, myocardial functions were assessed by measuring left ventricular developed pressure (LVDP), rate of left ventricular pressure development (dp/dt (max)), rate of left ventricular pressure decay (dp/dt (min)) and left ventricular end diastolic pressure (LVEDP) on an isolated Langendorff's heart preparation. Further, mean arterial blood pressure (MABP) was measured by using the tail-cuff method. Assessment of renal functions and lipid profile was carried out using a spectrophotometer. The administration of streptozotocin to rats produced persistent hyperglycaemia, dyslipidaemia and hypertension which consequently produced cardiac and renal dysfunction in 8 weeks. AVE0991 treatment produced cardio-renal protective effects, as evidenced by a significant increase in LVDP, dp/dt (max), dp/dt (min) and a significant decrease in LVEDP, BUN, and protein urea. Further, AVE-0991 treatment for the first time has been shown to reduce dyslipidaemia and produced antihyperglycaemic activity in streptozotocin-treated rats. However, MABP and creatinine clearance remained unaffected with AVE-0991 treatment. AVE-0991 produced cardio-renal protection possibly by improving glucose and lipid metabolism in diabetic rats, independent of its blood pressure lowering action.