Petalonia improves glucose homeostasis in streptozotocin-induced diabetic mice

The anti-diabetic potential of Petalonia binghamiae extract (PBE) was evaluated in vivo. Dietary administration of PBE to streptozotocin (STZ)-induced diabetic mice significantly lowered blood glucose levels and improved glucose tolerance. The mode of action by which PBE attenuated diabetes was investigated in vitro using 3T3-L1 cells. PBE treatment stimulated 3T3-L1 adipocyte differentiation as evidenced by increased triglyceride accumulation. At the molecular level, peroxisome proliferator-activated receptor γ (PPARγ) and terminal marker protein aP2, as well as the mRNA of GLUT4 were up-regulated by PBE. In mature adipocytes, PBE significantly stimulated the uptake of glucose and the expression of insulin receptor substrate-1 (IRS-1). Furthermore, PBE increased PPARγ luciferase reporter gene activity in COS-1 cells. Taken together, these results suggest that the in vivo anti-diabetic effect of PBE is mediated by both insulin-like and insulin-sensitizing actions in adipocytes.     

Effects of an alpha-glucosidase inhibitor, acarbose, on blood glucose and serum lipids in streptozotocin-induced diabetic rats

Effects of either a single dose or a long-term administration of an alpha-glucosidase inhibitor, acarbose, on blood glucose, cholesterol concentrations in serum lipoprotein fractions, triglycerides and free fatty acids were examined in streptozotocin-induced diabetic rats. In experiment 1, starch loading tests were performed with or without adding acarbose. The addition of acarbose (0.75 mg per kg of body weight or over) significantly reduced the elevation of blood glucose levels. In experiment 2, the animals were divided into three groups: Group A fed on a control diet, Group B fed on a diet containing 5 mg acarbose in 100 g of diet and Group C fed on a diet containing 20 mg acarbose in 100 g of diet. The food intake in Group C was significantly reduced by 22% as compared to Group A, while the food intake in Group B showed no change. The high dose of acarbose showed a tendency to lower fasting blood glucose levels, but the difference was statistically insignificant. However, postprandial glucose levels in Group C at each period examined and in Group B at 30 days were significantly lower than the counterparts in Group A. Acarbose caused a dose-dependent decrease in serum total cholesterol levels and HDL-cholesterol: total cholesterol ratios were elevated in Group B and C. Serum triglyceride levels in Group B and C were extremely lower than those in Group A on and after 20 days. These results indicate that the addition of acarbose to the diet induces a decrease in postprandial blood glucose levels and simultaneously causes an improvement in lipid metabolism of streptozotocin-induced diabetic rats.     

Ulva rigida improves carbohydrate metabolism, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats

This study was designed to investigate the effects of Ulva rigida, one of the green algae, on the lipid profile and oxidative–antioxidative systems in streptozotocin‐induced diabetic rats. Forty Wistar rats randomly divided into four groups: control (C), control + U. rigida extract (C + URE), diabetes (D) and diabetes + U. rigida extract (D + URE). U. rigida (2%) was administered in drinking water for 5 weeks after the induction of diabetes. U. rigida reduced the blood glucose, serum total cholesterol, triglyceride levels and plasma and tissue malondialdehyde (MDA) levels in the D + URE group. Insulin levels were significantly higher in the D + URE than those of the D group. Serum total cholesterol and tissue MDA levels were reduced in the C + URE group. Whole blood glutathione peroxidase and erythrocyte superoxide dismutase activities were higher in the D and C + URE groups compared with the C group. Paraoxonase and arylesterase activities were lower in the D group while U. rigida increased paraoxonase activities in C + URE and D + URE groups. This is the first study which showed U. rigida has antidiabetic and antihyperlipidemic effects and improves oxidative stress in diabetic rats. We conclude that U. rigida might have a potential use as a protective and/or therapeutic agent in diabetes mellitus. Copyright © 2011 John Wiley & Sons, Ltd.     

Effect of new and known 1,4-dihydropyridine derivatives on blood glucose levels in normal and streptozotocin-induced diabetic rats

Analysis of the effect of several 1,4-DHP Ca(2+) channel antagonists on experimental and clinical diabetes shows that structurally similar Ca(2+) channel antagonists can exert opposite effects on Ca(2+) influx, glucose homeostasis and insulin secretion. The influence of the Ca(2+) channel antagonists on pancreatic beta cell functions is dependent on lipophilicity, interactions with the cell membrane lipid bilayer, with SNAREs protein complexes in cell and vesicle membranes, with intracellular receptors, bioavailability and time of elimination from several organs and the bloodstream. In the present work we studied the effect at several doses of new compounds synthesized in the Latvian Institute of Organic Synthesis on blood glucose levels in normal and STZ-induced diabetic rats. The compounds tested were: 1,4-DHP derivatives cerebrocrast (1), etaftoron (2), OSI-1190 (3), OSI-3802 (4), OSI-2954 (5) and known 1,4-DHP derivatives: niludipine (6), nimodipine (7) and nicardipine (8) which possess different lipophilicities. Analysis of the structure-function relationships of the effect of 1,4-DHP derivatives on glucose metabolism showed that cerebrocrast could evoke qualitative differences in activity. Insertion of an OCHF(2) group in position 2 of the 4-phenylsubstituent and propoxyethylgroup R in ester moieties in positions 3 and 5 of the DHP structure, as well as an increase in the number of carbon atoms in the ester moiety, significantly modified the properties of the compound. Thereby cerebrocrast acquired high lipophilicity and membranotropic properties. Cerebrocrast, in a single administration at low doses (0.05 and 0.5 mg x kg(-1), p.o.), significantly decreased the plasma level of glucose in normal rats and in STZ-induced diabetic rats returned plasma glucose to basal levels. This effect was characterized by a slow onset and a powerful long-lasting influence on glucose metabolism, especially in STZ-induced diabetic rats.     

Iuteolin对糖尿病大鼠心脏功能的保护作用及其可能机制

目的：研究Iuteolin对链脲佐菌素诱导的Ⅰ型糖尿病大鼠心功能及心肌线粒体氧化应激的影响。方法：雄性SD大鼠,随机分成正常对照组,Iuteolin对照纽,糖尿病模型组,低剂量Iuteolin（10ms／（kg·d））灌胃治疗组,高剂量Iuteolin（100ms／（kg·d））灌胃治疗组。各组大鼠饲养8周后,测体重、血糖、心功能、左心室重量、心肌胶原含量及活性氧自由基（ROS）水平,分离心肌线粒体检测ROS水平、超氧化物歧化酶（SOD）活性及线粒体肿胀程度。结果：Iuteolin处理对糖尿病大鼠血糖无明显影响,但可减少糖尿病引起的体重下降。高剂量Iuteolin可显著减小糖尿病大鼠心室与体重比值,提高左室发展压,降低左室舒张末压。高剂量Iuteolin治疗后,糖尿病大鼠心肌ROS及胶原含量。心肌线粒体ROS水平与肿胀程度均明显下降,心肌线粒体SOD活性明显增加。结论：Iuteolin处理可显著改善糖尿病大鼠心功能．其机制可能与减轻心肌线粒体氧化应激及抑制线粒体肿胀有关。     

南瓜多糖对糖尿病大鼠血糖和血脂的影响

目的：研究南瓜多糖对糖尿病大鼠血糖和血脂的影响。方法：Wistar大鼠腹腔注射四氧嘧啶后。将成模的糖尿病大鼠根据血糖和体重随机分为糖尿病组、消渴丸组和南瓜多糖组,同时设立正常对照组,并分别给予蒸馏水、消渴丸和南瓜多糖灌胃,每周测量体重一次,四周后测定空腹血糖、血清总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白和游离脂肪酸的含量。结果：糖尿病组大鼠体重下降,血糖显著升高,甘油三酯、总胆固醇、低密度脂蛋白和游离脂肪酸含量显著增加,而高密度脂蛋白含量显著降低;补充南瓜多糖和消渴丸后,体重逐渐增加,血糖显著下降,总胆固醇、甘油三酯、低密度脂蛋白和游离脂肪酸含量显著降低,高密度脂蛋白含量显著升高,并且南瓜多糖的降糖降脂效果优于消渴丸。结论：南瓜多糖能增加体重,降低糖尿病大鼠血糖、血脂,对糖尿病及其并发症有一定的作用。     

The effect of pre-germinated brown rice intake on blood glucose and PAI-1 levels in streptozotocin-induced diabetic rats

Effects of pre-germinated brown rice (PGBR) on streptozotocin-induced diabetic rats were studied. The feeding of a PGBR diet to diabetic rats ameliorated the elevation of blood glucose and PAI-1 concentrations significantly, and tended to decrease the plasma lipid peroxide concentrations in comparison with rats fed a white rice diet. These results suggest that intake of PGBR instead of white rice is effective for the prevention of diabetic vascular complications.     

Metformin reduces blood pressure and restores endothelial function in aorta of streptozotocin-induced diabetic rats

Effect of metformin treatment on blood pressure, endothelial function and oxidative stress in streptozotocin (STZ)-induced diabetes in rats was studied. In vitro effect of metformin on vascular reactivity to various agonist in the presence of metformin in untreated nondiabetic and STZ-diabetic rats were also studied. Sprague-Dawley rats were randomized into nondiabetic and STZ-diabetic groups. Rats were further randomized to receive metformin (150 mg/kg) or vehicle for 4 weeks.Metformin treatment reduced blood pressure without having any significant effect on blood glucose level in STZ-diabetic rats. Enhanced phenylephrine (PE)-induced contraction and impaired acetylcholine (Ach)-induced relaxation in STZ-diabetic rats were restored to normal by metformin treatment. Enhanced Ach-induced relaxation in metformin-treated STZ-diabetic rats was blocked due to pretreatment with 100 μM of Nω-nitro-l-arginine-methyl ester (l-NAME) or 10 μM of methylene blue but not 10 μM of indomethacin. Metformin treatment significantly increased antioxidant enzymes and reduced lipid peroxidation in STZ-diabetic rats. In vitro studies in aortic rings of untreated nondiabetic and STZ-diabetic rats showed that the presence of higher concentration of metformin (1 mM and 10 mM) significantly reduced PE-induced contraction and increased Ach-induced relaxation. Metformin per se relaxed precontracted aortic rings of untreated nondiabetic and STZ-diabetic rats in a dose-dependent manner. Pretreatment with l-NAME or removal of endothelium blocked metformin-induced relaxation at lower concentration (up to 30 μM) but not at higher concentration (above 30 μM). Metformin-induced relaxation was blocked in the presence of 1 mM of 4-aminopyridine, or 1 mM of tetraethylammonium but not in the presence of 100 μM of barium ion or 10 μM of glybenclamide. The restored endothelial function along with direct effect of metformin on aortic rings and reduced oxidative stress contributes to reduced blood pressure in STZ-diabetic rats. From the present study, it can be concluded that metformin administration to STZ-diabetic rats lowers blood pressure, and restores endothelial function.     

Effect of tangeretin,a polymethoxylated flavone on glucose metabolism in streptozotocin-induced diabetic rats

The present study was designed to evaluate the antihyperglycemic potential of tangeretin on the activities of key enzymes of carbohydrate and glycogen metabolism in control and streptozotocin induced diabetic rats. The daily oral administration of tangeretin (100 mg/kg body weight) to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and increase in the levels of insulin and hemoglobin. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver of diabetic rats were significantly reverted to near normal levels by the administration of tangeretin. Further, tangeretin administration to diabetic rats improved hepatic glycogen content suggesting the antihyperglycemic potential of tangeretin in diabetic rats. The effect produced by tangeretin on various parameters was comparable to that of glibenclamide – a standard oral hypoglycemic drug. Thus, these results show that tangeretin modulates the activities of hepatic enzymes via enhanced secretion of insulin and decreases the blood glucose in streptozotocin induced diabetic rats by its antioxidant potential.     

Impaired ascorbic acid metabolism in streptozotocin-induced diabetic rats

Ascorbic acid (AA) metabolism in streptozotocin (STZ)-induced diabetic rats was determined by examining urinary excretion, renal reabsorption, reductive regeneration, and biosynthesis of AA at 3 and 14 days after STZ administration. AA concentrations in the plasma, liver, and kidney of the diabetic rats were significantly lower than those of controls on d 3, and decreased further as the diabetic state continued. Hepatic AA regeneration significantly decreased in the diabetic rats on d 3 in spite of increased gene expressions of AA regenerating enzymes and was further reduced on d 14. Hepatic activity of L-gulono-gamma-lactone oxidase, a terminal enzyme of hepatic AA biosynthesis, also decreased significantly on d 3 and decreased further on d 14. Urinary excretion of AA was significantly increased on d 3, with an increase in urine volume but no change in gene expressions of renal AA transporters (SVCT1 and SVCT2). Urinary excretion of AA was normalized on d 14. The results suggest that impaired hepatic and renal regeneration, as well as increased urinary excretion and impaired hepatic biosynthesis of AA, contributed to the decrease in AA in plasma and tissues of STZ-induced diabetic rats.     

Long-term taurine supplementation reduces mortality rate in streptozotocin-induced diabetic rats

Summary. Oxidative stress is implicated in the pathogenesis of diabetes mellitus. Taurine and vitamin E+selenium supplementation has some benefits in experimental models of diabetes mellitus. This study evaluates whether taurine and vitamin E+selenium supplementations reduce a hard end-point such as mortality due to diabetes. Streptozotocin-induced diabetic rats were fed with standard diet or taurine (5%, w/w) or vitamin E (500UI/Kg)+selenium (8mg/Kg) enriched diets. Taurine significantly decreased mortality rate (p<0.04), while vitamin E failed to increase survival. In the late phase of the disease, taurine significantly decreased glycaemia, being vitamin E ineffective. No correlation between glycaemia and survival was found. None of supplementations modified body weight. Thus, only taurine decreases the mortality rate and glycaemia. These results encourage new research in the field, since classical hypoglycaemic agents are unable to decrease mortality in diabetic patients.     

Galangin,a dietary flavonoid,improves antioxidant status and reduces hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats

Objective: To examine the effect of galangin on hyperglycemia-mediated oxidative stress in streptozotocin (STZ)-induced diabetic rats.

Methods: Diabetes was induced by intraperitoneal administration of low-dose STZ (40?mg/kg body weight (BW)) into male albino Wistar rats. Galangin (8?mg/kg BW) or glibenclamide (600?µg/kg BW) was given orally, once daily for 45 days to normal and STZ-induced diabetic rats.

Results: Diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes. The levels of insulin and non-enzymatic antioxidants (vitamin C, vitamin E, reduced glutathione) and the activity of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase (GST)) were decreased significantly in diabetic control rats. These altered plasma glucose, insulin, lipid peroxidation products, enzymatic and non-enzymatic antioxidants ions were reverted to near-normal level after the administration of galangin and glibenclamide.

Conclusion: The present study shows that galangin decreased oxidative stress and increased antioxidant status in diabetic rats, which may be due to its antidiabetic and antioxidant potential.     

Shikonin increases glucose uptake in skeletal muscle cells and improves plasma glucose levels in diabetic Goto-Kakizaki rats

Background

There is considerable interest in identifying compounds that can improve glucose homeostasis. Skeletal muscle, due to its large mass, is the principal organ for glucose disposal in the body and we have investigated here if shikonin, a naphthoquinone derived from the Chinese plant Lithospermum erythrorhizon, increases glucose uptake in skeletal muscle cells.

Methodology/Principal Findings

Shikonin increases glucose uptake in L6 skeletal muscle myotubes, but does not phosphorylate Akt, indicating that in skeletal muscle cells its effect is medaited via a pathway distinct from that used for insulin-stimulated uptake. Furthermore we find no evidence for the involvement of AMP-activated protein kinase in shikonin induced glucose uptake. Shikonin increases the intracellular levels of calcium in these cells and this increase is necessary for shikonin-mediated glucose uptake. Furthermore, we found that shikonin stimulated the translocation of GLUT4 from intracellular vesicles to the cell surface in L6 myoblasts. The beneficial effect of shikonin on glucose uptake was investigated in vivo by measuring plasma glucose levels and insulin sensitivity in spontaneously diabetic Goto-Kakizaki rats. Treatment with shikonin (10 mg/kg intraperitoneally) once daily for 4 days significantly decreased plasma glucose levels. In an insulin sensitivity test (s.c. injection of 0.5 U/kg insulin), plasma glucose levels were significantly lower in the shikonin-treated rats. In conclusion, shikonin increases glucose uptake in muscle cells via an insulin-independent pathway dependent on calcium.

Conclusions/Significance

Shikonin increases glucose uptake in skeletal muscle cells via an insulin-independent pathway dependent on calcium. The beneficial effects of shikonin on glucose metabolism, both in vitro and in vivo, show that the compound possesses properties that make it of considerable interest for developing novel treatment of type 2 diabetes.     

Spider silk fibroin enhances insulin secretion and reduces blood glucose levels in diabetic mice

Fibroin silk proteins make up the cocoons of silkworms and spider webs and are rich in glycine and alanine residues. Recent studies have shown that silk fibroin hydrolysate from silkworms improves blood glucose and lipid metabolism. In the present study, we investigated the anti-diabetic effects of spider silk fibroin protein in type 2 diabetic mice. Recombinant AvMaSp-R, which consists of the 240 amino acid repetitive domain of major ampullate silk protein (AvMaSp) from the spider Araneus ventricosus, was produced in baculovirus-infected insect cells. We tested the effects of oral AvMaSp-R administration on serum insulin and blood glucose levels in diabetic mice and found that AvMaSp-R increases serum insulin levels and reduces blood glucose levels in diabetic mice. Consequently, our results are the first to provide evidence that silk fibroin protein from spiders enhances insulin secretion, which leads to reduced blood glucose levels in type 2 diabetic mice.     

Capsiate improves glucose metabolism by improving insulin sensitivity better than capsaicin in diabetic rats

Red peppers and red pepper paste are reported to have anti-obesity, analgesic and anti-inflammatory effects in animals and humans due to the capsaicin in red pepper. We investigated whether consuming capsaicin and capsiate, a nonpungent capsaicin analogue, modifies glucose-stimulated insulin secretion, pancreatic β-cell survival and insulin sensitivity in 90% pancreatectomized (Px) diabetic rats, a moderate and non-obese type 2 diabetic animal model. Px diabetic rats were divided into 3 treatment groups: 1) capsaicin (Px-CPA), 2) capsiate (Px-CPI) or 3) dextrose (Px-CON) and provided high fat diets (40 energy % fat) containing assigned components (0.025% capsaicin, capsiate, or dextrose) for 8 weeks. Both capsaicin and capsiate reduced body weight gain, visceral fat accumulation, serum leptin levels and improved glucose tolerance without modulating energy intake in diabetic rats. In comparison to the control, both capsaicin and capsiate potentiated first and second and phase insulin secretion during hyperglycemic clamp. Both also increased β-cell mass by increasing proliferation and decreasing apoptosis of β-cells by potentiating insulin/IGF-1 signaling. However, only capsiate enhanced hepatic insulin sensitivity during euglycemic hyperinuslinemic clamp. Capsiate reduced hepatic glucose output and increased triglyceride accumulation in the hyperinsulinemic state and capsiate alone significantly increased glycogen storage. This was related to enhanced pAkt→PEPCK and pAMPK signaling. Capsaicin and capsiate reduced triglyceride storage through activating pAMPK. In conclusion, capsaicin and capsiate improve glucose homeostasis but they differently enhance insulin sensitivity in the liver, insulin secretion patterns, and islet morphometry in diabetic rats. Capsiate has better anti-diabetic actions than capsaicin.     

Adrenomedullin improves cardiac function and prevents renal damage in streptozotocin-induced diabetic rats

Adrenomedullin (AM) is a potent vasodilating peptide and is involved in cardiovascular and renal disease. In the present study, we investigated the role of AM in cardiac and renal function in streptozotocin (STZ)-induced diabetic rats. A single tail-vein injection of adenoviral vectors harboring the human AM gene (Ad.CMV-AM) was administered to the rats 1-wk post-STZ treatment (65 mg/kg iv). Immunoreactive human AM was detected in the plasma and urine of STZ-diabetic rats treated with Ad.CMV-AM. Morphological and chemical examination showed that AM gene delivery significantly reduced glycogen accumulation within the hearts of STZ-diabetic rats. AM gene delivery improved cardiac function compared with STZ-diabetic rats injected with control virus, as observed by decreased left ventricular end-diastolic pressure, increased cardiac output, cardiac index, and heart rate. AM gene transfer significantly increased left ventricular long axis (11.69 +/- 0.46 vs. 10.31 +/- 0.70 mm, n = 10, P < 0.05) and rate of pressure rise and fall (+6,090.1 +/- 597.3 vs. +4,648.5 +/- 807.1 mmHg/s), (-4,902.6 +/- 644.2 vs. -3,915.5 +/- 805.8 mmHg/s, n = 11, P < 0.05). AM also significantly attenuated renal glycogen accumulation and tubular damage in STZ-diabetic rats as well as increased urinary cAMP and cGMP levels, along with increased cardiac cAMP and Akt phosphorylation. We also observed that delivery of the AM gene caused an increase in body weight along with phospho-Akt and membrane-bound GLUT4 levels in skeletal muscle. These results suggest that AM plays a protective role in hyperglycemia-induced glycogen accumulation and cardiac and renal dysfunction via Akt signal transduction pathways.     

Renal glucose reabsorption during hypertonic glucose infusion in female streptozotocin-induced diabetic rats.

Information regarding the renal glucose transport capacity in diabetes mellitus is limited. These data are needed because two weeks following injection of streptozotocin (STZ), mRNA and protein levels of the glucose transporter, GLUT2, are upregulated in the proximal tubule of the rat. Therefore, we measured renal glucose transport and GLUT2 protein levels in female control rats, and in rats one (STZ-1), two (STZ-2), and three weeks (STZ-3) after STZ injection (65 mg kg(-1), i.p.). Progressive amounts of glucose were infused into anesthetized rats via the femoral vein and renal clearances collected. The amount of glucose reabsorbed, factored by the glomerular filtration rate (GFR) was significantly greater in STZ-3 rats compared with all other groups. In addition, the amount of glucose reabsorbed factored by the amount of glucose filtered was decreased in STZ-1 and STZ-2 compared with controls but was increased in STZ-3. By contrast, renal GLUT2 levels were elevated in all the STZ-treated rats. These data suggest that other factors, functioning either in conjunction with or independent of GLUT2, are required to support an elevated renal glucose transport capacity.     

Oral administration of sodium tungstate improves cardiac performance in streptozotocin-induced diabetic rats

Normalization of hyperglycemia and hyperlipidemia is an important objective in preventing diabetes-induced cardiac dysfunction. Our study investigated the effects of sodium tungstate on cardiac performance in streptozotocin-induced (STZ) diabetic rats based on its potential antidiabetic and antioxidant activity. Male Wistar rats were made STZ-diabetic and then treated with tungstate in their drinking water for 9 weeks. Body mass, food and fluid intake, plasma glucose, insulin, triglyceride, and free fatty acids levels were measured. At the termination of the study period, an oral glucose tolerance test (OGTT) was performed, and cardiac performance was evaluated using an isolated working heart apparatus. Tungstate-treated STZ-diabetic rats showed a significant reduction in fluid and food intake, plasma glucose, triglycerides, and free fatty acid levels, and improved tolerance to glucose in OGTT, owing to tungstate-mediated enhancement of insulin activity rather than increased insulin levels. Left ventricular pressure development, the rate of contraction (+dP/dT), and the rate of relaxation (-dP/dT) were significantly improved in tungstate-treated diabetic rats. Apart from a decreased rate of body mass gain, no other signs of toxicity or hypoglycemic episodes were observed in tungstate-treated rats. This study extends previous observations on the antidiabetic activities of tungstate, and also reports for the first time the salutary effects in preventing diabetic cardiomyopathy.