LPS-induced neutrophilic inflammation and Bcl-2 expression in metaplastic mucous cells

Our previous studies show that Bcl-2, a regulator of apoptosis, may be involved in the reduction of mucous cell metaplasia (MCM) during recovery from inflammatory responses. The present study was to determine whether neutrophilic inflammation mediates Bcl-2 expression in mucous cells. Rats were intratracheally instilled with 50-1000 microg of LPS. The number of neutrophils recovered by bronchoalveolar lavage (BAL) increased with the dose of LPS, and the percentage of Bcl-2-expressing cells increased with the numbers of neutrophils in the BAL. Depletion of neutrophils did not reduce MCM, but the percentage of Bcl-2-positive cells increased 1.8-fold in neutrophil-depleted compared with controls. Injection of rats with bezafibrate, an inducer of cytochrome P-450, doubled the number of neutrophils in the BAL, decreased MCM twofold compared with vehicle-injected controls, and reduced Bcl-2 expression. Bcl-2 mRNA levels decreased in a tracheal epithelial cell line treated with bezafibrate. These data demonstrate that Bcl-2 expression is independent of the number of neutrophils in the BAL and that bezafibrate may directly reduce Bcl-2 expression in epithelial cells.     

链尿佐菌素加高糖高脂饮食复制大鼠2型糖尿病模型

目的链尿佐菌素加高糖高脂饮食诱导大鼠2型糖尿病模型的建立。方法SD雄性大鼠高糖高脂饲料喂养3周后,采血检测空腹血糖及血清胰岛素,按25mg/g体重剂量一次性腹腔内注射链尿佐菌素,3d后,行糖耐量实验,对糖耐量异常大鼠继续喂以高糖高脂饲料,在第2、第4周再两次采血检测糖尿病鼠空腹血糖及血清胰岛素。结果与对照组比较,高糖高脂喂养大鼠血清胰岛素明显上升（P〈0.01）,但血糖无变化（P〉0.05）,糖尿病鼠血糖及血清胰岛素均显著的高于对照组（P〈0.01）。结论高糖高脂喂养能致大鼠明显的高胰岛素血症,辅以小剂量一次性注射链尿佐菌素而造成的糖耐量异常,可成功复制出2型糖尿病大鼠模型。     

粗根荨麻水提取部分对佐剂性关节炎大鼠腹腔巨噬细胞分泌TNF—α及PGE2的影响

观察滇产粗根荨麻水提取部分对佐剂性关节炎(adjuvant arthritis,AA)大鼠腹腔巨噬细胞(peritoneal macrophages,PMcp)分泌肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)及前列腺素E2(prostaglandin E2,PGE2)的影响.建立大鼠佐剂性关节炎模型,Ur水提取部分连续灌胃给药14或21 d后分次获取大鼠腹腔巨噬细胞,脂多糖(lipopolysacehafide,LPS)诱导大鼠腹腔巨噬细胞,用酶联免疫吸附法检测培养上清液中TNF-α及PGE2水平.从大鼠腹腔巨噬细胞TNF-α及PGE2分泌较正常组升高,Ur水提取部分(400,200 mg/kg)对LPS诱导的AA大鼠腹腔巨噬细胞分泌TNF-α及PGE2水平有明显抑制作用.滇产粗根荨麻水提取部分对佐剂性关节炎的治疗作用可能与其抑制腹腔巨噬细胞分泌TNF-α及PGE2有关.     

Rapid pacing-induced preconditioning is recaptured by farnesol treatment in hearts of cholesterol-fed rats: Role of polyprenyl derivatives and nitric oxide

Sodium selenate, administered intraperitoneally (i.p.), resulted in an improvement in glucose tolerance in treated diabetic rats. Fed rat plasma glucose levels were reduced by selenate treatment in streptozotocin diabetic rats. The lowest values of blood glucose were reached within 3 weeks of beginning the treatment. Food and fluid consumption was reduced in treated compared to untreated diabetic rats. Diabetic treated rats did not release insulin in response to a glucose challenge and insulin release in response to a challenge was markedly reduced in control treated rats. Assessment of heart function using a working heart apparatus showed that treated diabetic rats with improved blood glucose levels had normal heart function at 8 weeks of diabetes in contrast to hearts from non-treated diabetics. This study extends previous observations on the in vivo insulin-like effects of sodium selenate.     

Adoptive transfer of acute lung injury

In this study, we describe a novel adoptive transfer protocol to study acute lung injury in the rat. We show that bronchoalveolar lavage (BAL) cells isolated from rats 5 h after intratracheal administration of lipopolysaccharide (LPS) induce a lung injury when transferred to normal control recipient rats. This lung injury is characterized by increased alveolar-arterial oxygen difference and extravasation of Evans blue dye (EBD) into lungs of recipient rats. Recipient rats receiving similar numbers of donor cells isolated from healthy rats do not show adverse changes in the alveolar-arterial oxygen difference or in extravasation of EBD. The adoptive transfer-induced lung injury is associated with increased numbers of neutrophils in the BAL, the levels of which are similar to the numbers observed in BAL cells isolated from rats treated for 5 h with LPS. As an indicator of BAL cell activation, donor BAL cell inducible nitric oxide synthase (iNOS) expression was compared with BAL cell iNOS expression 48 h after adoptive transfer. BAL cells isolated 5 h after LPS administration expressed iNOS immediately after isolation. In contrast, BAL cells isolated 48 h after adoptive transfer did not express iNOS immediately after isolation but expressed iNOS following a 24-h ex vivo culture. These findings indicate that the activation state of donor BAL cells differs from BAL cells isolated 48 h after adoptive transfer, suggesting that donor BAL cells may stimulate migration of new inflammatory cells into the recipient rats lungs.     

Intestinal zinc transport: influence of streptozotocin-induced diabetes, insulin and arachidonic acid

The influence of arachidonic acid (AA) on the zinc flux rates of jejunal segments, isolated from streptozotocin-induced diabetic rats injected with saline or with insulin, was investigated using an Ussing chamber technique. Although the zinc flux rates from mucosa-to-serosa (Jms) of normal rats were inhibited by addition of 5 microM AA to the jejunal segment bathing medium (46.4 +/- 5.0 vs 32.6 +/- 4.3 nmol/hr/cm2), AA had no effect on the Jms of diabetic rats either with or without insulin treatment. Induction of diabetes also significantly reduced Jms (46.4 +/- 5.0 vs 22.1 +/- 4.9 nmol/hr/cm2), but 3 day insulin treatment (NPH 8 U/Kg/day subcutaneously) did not reverse this effect (29.2 +/- 5.1 nmol/hr/cm2). Addition of AA to the serosal side did not significantly alter the zinc flux rate from serosa-to-mucosa (Jsm) in either control, diabetic or diabetic rats treated with insulin. The net zinc absorption rate (Jnet) of jejunal segments was decreased in diabetic rats compared to controls (13.2 +/- 3.0 vs -0.7 +/- 2.1 nmol/hr/cm2), but normalization of blood glucose with 3 day insulin treatment did not increase Jnet. Addition of AA was associated with a tendency to increase zinc uptake capacity. This change reached statistical significance in insulin treated diabetic rats. Short-circuit current (Isc) for diabetic rats was increased compared to controls but addition of AA to the mucosal side bathing medium decreased Isc in all groups. The results indicate that the zinc flux rate in the small intestine of streptozotocin-induced diabetic rats is decreased, that zinc uptake capacity of the small intestine does not directly reflect the zinc flux rate across the small intestine, and that AA or one of its metabolites may play a significant role in the control of the zinc flux across the intestinal epithelium.     

Anti-hyperglycemic activity of zinc plus cyclo (his-pro) in genetically diabetic Goto-Kakizaki and aged rats

We previously reported that treatment of streptozotocin-induced diabetic rats with zinc plus cyclo (his-pro) (CHP) decreased fed blood glucose levels and water intake. The present study was conducted to examine the dose-dependent, acute, and chronic treatment effects of CHP on oral glucose tolerance (OGT), fed blood glucose levels, water intake, and plasma insulin levels in young and aged Sprague-Dawley (S-D) rats, nondiabetic Wistar rats, and genetically diabetic Goto-Kakizaki (G-K) rats. Acute gastric gavage of 10 mg zinc plus 1.0 mg CHP/kg body weight significantly improved OGT in 4- and 13-month-old nondiabetic S-D rats and in 2-month-old diabetic G-K rats. Young S-D and G-K rats returned to pretreatment OGT values 1 week after acute gavage of zinc plus CHP (ZC), but improved OGT values persisted for at least 1 week after gavage in aged S-D rats. OGT values and fed blood glucose decreased to the greatest extent among other treatments when G-K rats were given free access to drinking water containing 1.0 to 1.5 mg CHP/L plus 10 mg zinc/L for 2 weeks. Although food and water intake showed a tendency to decrease, no statistically significant differences were observed in young G-K rats. Plasma insulin levels and blood glucose levels in both normal and diabetic G-K rats decreased with 2-week treatment with ZC. To test the direct effects of ZC on muscle tissue, we observed the effect of various doses of ZC on normal and G-K rat muscle slices. The optimal level of CHP alone for maximal muscle glucose uptake in muscle slices from normal rats was 10 microg/mL and 5.0 microg/mL in G-K rats, and ZC stimulated glucose uptake. However, no statistically significant difference was demonstrated between normal and G-K rat tissues in this study. These results indicate that oral intake of an optimal dose of ZC stimulates blood glucose metabolism, probably by stimulating muscle glucose utilization.     

Enhanced in vivo sensitivity of vanadyl-treated diabetic rats to insulin

Vanadium has been reported to have insulin-like properties and has recently been demonstrated to be beneficial in the treatment of diabetic animals. In the present study, concentration dependence of the therapeutic effects of vanadium and the nature of interaction under in vivo conditions between vanadium and insulin were examined in streptozotocin-diabetic rats. During a 2-week period, blood glucose levels in all treated animals were decreased. At higher concentrations of vanadyl this decrease was greater and more rapid, and remained consistently lower for the entire treatment period. Daily intake of vanadyl, however, reached a similar steady state in all groups. Acute administration of submaximal doses of insulin, which had minimal effects in untreated diabetic rats, lowered blood glucose concentrations in vanadyl-treated and vanadyl-withdrawn animals to control levels. Chronic treatment of streptozotocin-diabetic rats with submaximal levels of vanadyl and insulin, ineffective alone, also produced significant decreases in blood glucose levels when used in combination. Finally, the insulin dosage required to maintain a nonglycosuric state in spontaneously diabetic (BB) rats was reduced in the presence of vanadyl. These studies indicate that chronic oral vanadyl treatment (a) produces a concentration-related lowering of blood glucose in diabetic rats, (b) potentiates the in vivo glucose lowering effects of acute and chronic administrations of insulin in streptozotocin-diabetic rats, and (c) substitutes for, or potentiates, the effects of chronic insulin therapy in spontaneously diabetic BB rats.     

A model for evaluation of the peroral insulin therapy: short-term treatment of alloxan diabetic rats with oral water-in-oil-in-water insulin emulsions.

Alloxan diabetic rats with fasting blood glucose levels above 300 mg/100 ml were treated with oral administration of water-in-oil-in-water (W/O/W) insulin emulsions at a dose of 50 U/100 g body weight, three times daily for 10 to 14 days. The course of diabetes was followed by determinations of glucose levels in blood and urine. During treatment with oral W/O/W insulin emulsions, daily excretion of urinary glucose decreased by about 30 to 40% (2 to 3 g/day) in all of the five rats studied, and returned to the pre-treatment levels after the treatment being discontinued. During treatment, a significant reduction in fasting blood glucose levels was observed in 4 out of 5 rats, giving the decrease by 18 to 44%. Quantitative estimates suggested that the effectiveness of 50 U/100 g of oral W/O/W insulin emulsions was comparable to that after intramuscular regular insulin at a dose of 0.5 U/100 g. Although oral W/O/W insulin emulsions are still of low efficiency, these results would indicate that diabetes can be controlled by effective oral insulin preparations.     

Effects of fluticasone propionate inhalation on levels of arachidonic acid metabolites in patients with chronic obstructive pulmonary disease

BACKGROUND: In smoking COPD patients the bronchoalveolar lavage (BAL) fluid contains high numbers of inflammatory cells. These cells might produce arachidonic acid (AA) metabolites, which contribute to inflammation and an increased bronchomotor tone. AIMS: To investigate levels of AA metabolites in BAL fluid, before and after inhaled glucocorticoid therapy: fluticasone propionate (FP) 1 mg per day, or placebo. METHODS: A double-blind placebo controlled trial lasting six months. COPD patients were selected by clinical criteria and the presence of bronchial hyper-responsiveness (BHR). Lung function was recorded and in BAL fluid we counted cell numbers and measured LTB4, LTC4/D4/E4, PGE2, 6kPGF1alpha, PGF2alpha and TxB2. A control group consisted of asymptomatic smokers (n=6). RESULTS: Paired data were obtained from 9 FP treated and 11 placebo patients. BAL cells were almost exclusively alveolar macrophages. In patients and controls both cellularity and levels of AA metabolites were equal Cell numbers did not change after treatment. Statistically significant decreases after FP therapy were noticed for PGE2 (30%), 6kPGF1alpha (41%) and PGF2alpha (54%). CONCLUSIONS: In COPD, the capability of inflammatory cells to produce certain AA metabolites was decreased after inhaled FP treatment. This result is discussed in its relation to clinical effects, the influence of smoking, and the results of an earlier, similar study in asthma patients.     

Chronic Cobalt Treatment Decreases Hyperglycemia in Streptozotocin-Diabetic Rats

Diabetes is a metabolic disorder characterized by elevated blood glucose levels. Although conventional treatments such as insulin and other drugs reduce blood glucose, there is still a therapeutic need for effective orally administered drugs. Trace elements like vanadium and tungstate have been successfully demonstrated to reduce blood glucose in experimental diabetes with minimal chronic complications. We investigated the anti-hyperglycemic effects of cobalt in streptozotocin-diabetic rats. Normal and diabetic rats were provided with drinking water containing 3.5 mM cobalt chloride for three weeks followed by 4 mM for four weeks. Body weights and fluid consumption were monitored on a daily basis, while food intake was recorded twice every week. Prior to termination, an oral glucose tolerance test was performed on the animals. Diabetic rats lost significant body weight (357 ± 2 gm) compared to controls (482 ± 3 gm). Body weight was further reduced by cobalt treatment (290 ± 2 gm). Although it was difficult to establish a dosing regimen without weight loss, food and fluid consumption in cobalt-treated diabetic rats improved significantly compared to untreated diabetics. Plasma glucose levels were significantly reduced with reference to diabetic controls (29.3 ± 0.9 mM) by the fourth week to a lower but still hyperglycemic level (13.6 ± 3.4 mM). Cobalt-treated diabetic rats demonstrated an enhanced ability to clear a glucose load compared to untreated diabetics. Cobalt treatment neither affected the feeding and drinking patterns nor plasma glucose in normoglycemic animals although body weights decreased compared to untreated controls. We conclude that chronic cobalt treatment decreases plasma glucose levels in STZ-diabetic rats and improves tolerance to glucose.     

Effect of sakuranin on carbohydrate-metabolizing enzyme activity modifications in streptozotocin-nicotinamide-induced diabetic wistar rats

This study is to assess the glucose lowering activity of sakuranin in diabetes induced rats by streptozotocin (STZ) and nicotinamide (NA). Diabetic rats were treated sakuranin for 45 days (20, 40, 80 mg/kg) by orally. Sakuranin (80 mg/kg body weight) was normalized the changes of abnormal blood glucose plasma glucose and plasma insulin levels. Hence, we have continued the further research with this active dose of 80 mg/kg sakuranin. The plasma glucose and glycosylated hemoglobin (HbA₁c) reduced and insulin, glycogen and hemoglobin levels increased by Sakuranin administration in diabetic rats. Additionally, hexokinase and glucose-6-phophate dehydrogenase activities increased and glucose-6-phosphatase and fructose-1,6-bisphosphatase activities decreased in diabetic condition while administration of treated compound. In this observed result signified that sakuranin may have potential role of diabetic condition rats by evidenced with reducing glucose and increasing insulin and also protect the carbohydrate metabolic changes.     

Evidence for a deficient pancreatic beta-cell response in a rat model of hyperthyroidism

To clarify mechanism behind the abnormal glucose tolerance, observed in hyperthyroidism, we studied genomic and nongenomic effects of thyroid hormone on insulin secretion using a rat model of hyperthyroidism. Male Sprague-Dawley rats were intraperitoneally injected with vehicle, low (100 microg/kg) or high dose (600 microg/kg) of thyroxin (T(4)) for 2 weeks. Rats treated with high dose, but not low dose, of T(4), showed an increase in serum T(3) levels, and a decrease in body weight as compared to control rats. In rats treated with either dose of T(4), fasting blood glucose levels were increased, but serum insulin levels were similar to those of controls. After an oral glucose load, blood glucose levels were increased in rats treated with high dose, but not low dose, of T(4). Serum insulin levels after the oral glucose load were decreased in rats treated with either dose of T(4). After an intravenous glucose load, blood glucose levels were comparable among groups, but serum insulin levels tended to be low in T(4)-treated rats. Steady-state blood glucose levels were comparable among groups. The insulin secretory responses to high glucose (20mM) or arginine (10mM) of the isolated pancreas was decreased in rats treated with high dose, but not low dose, of T(4). Mean insulin secretory response to glucose and arginine were decreased by 40.1% and by 60.4% in high-dose-T(4)-treated rats. Addition of T(3) in the perfusion medium decreased glucose-induced insulin release. Ratios of proinsulin mRNA levels to beta-actin mRNA were decreased in the islets of T(4)-treated rats (0.45 +/- 0.07 vs control 0.61 +/- 0.03, p < 0.05). Levels of TR (thyroid hormone nuclear receptor) alpha1 + cErb Aalpha2 mRNA, but not TRbeta1, were decreased in the pancreatic islets of T(4)-treated rats. Calculated islet area was increased, but the number of beta-cells determined immunohistochemically was not increased in T(4)-treated rats, nor the volume density of insulin positive islets. We concluded that a deficient pancreatic beta-cell response to glucose, rather than insulin resistance, was responsible for abnormal glucose tolerance in this model of hyperthyroidism. Thyroid hormone causes a decrease in glucose-induced insulin secretion. We observed nongenomic and genomic effects of thyroid hormone on glucose-induced insulin secretion.     

Controlled release of modified insulin glargine from novel biodegradable injectable gels

The objective of this study was to investigate the duration of biological effects of modified insulin glargine released from a novel biodegradable injectable gel in type II diabetic Zucker diabetic fatty (ZDF) rats. Modified insulin glargine was purified from the marketed formulation by process of dialysis followed by freeze-drying, and the purity was confirmed by the single peak, corresponding to insulin glargine in the HPLC chromatogram. To determine and to compare the biological activity of purified insulin glargine with marketed formulation, it was suspended in isotonic saline solutions and administered subcutaneously to ZDF rats at a dose of 10 IU/kg of insulin and the blood glucose levels were measured. The blood glucose levels of ZDF rats after a subcutaneous injection of a suspension of purified insulin glargine decreased below 200 mg/dL within 2 h and remained at this level up to 6 h, then steadily raised above 400 mg/dL in 12 h. Insulin glargine particles were loaded into a novel biodegradable injectable gel formulation prepared from a blend of polylactic-co-glycolic acid (PLGA) and biocompatible plasticizers. Approximately 0.1 mL of insulin glargine-loaded gel prepared with PLGA was administered subcutaneously to the ZDF rats, and blood glucose levels were measured. The PLGA gel formulations prepared with insulin glargine particles had duration of action of 10 days following a single subcutaneous injection. The addition of zinc sulfate to the formulations prepared with purified insulin glargine particles further slowed down the drop in blood glucose concentrations.     

Effects of prostaglandins and of leukotriene C4 on the metabolism of labelled glucose in uteri isolated from ovariectomized-diabetic rats. Influences of 17-beta-estradiol and of insulin.

The influences of exogenous PGE1, PGE2, PGF2 alpha, LTC4 and insulin (INS) on glucose oxidation in uterine strips isolated from ovariectomized-diabetic (OVD) and ovariectomized-estrogenized-diabetic (OVED) rats, were studied. The spayed animals were made diabetic by a single injection of streptozotocin (65 mg.kg-1 body weight). The effects of prostaglandins were studied in the presence of indomethacin (INDO) in the incubation medium and the effects of LTC4 in the presence of INDO and nordihydroguaretic acid (NDGA). These procedures were followed in order to avoid the possible influences of endogenous derivatives of arachidonic acid formed by the activity of cyclooxygenase and of lipoxygenases. INDO and NDGA did not modify significantly the formation of 14CO2 from U-14C-glucose in uteri from OVD and from OVED rats. INS (0.5 U.ml-1) augmented significantly labelled glucose metabolism, both in OVD as well as in OVED rats. On the other hand, added PGE1, PGE2, PGF2 alpha or LTC4 failed to alter glucose metabolism in uteri from OVD rats. Only PGE1 was able to increase significantly (p less than 0.05) 14CO2 production from labelled glucose in uterine strips from OVED rats. In OVD rats the stimulatory action of INS on uterine glucose metabolism was significantly enhanced by exogenous PGE1, but not modified by PGE2, by PGF2 alpha or by LTC4. PGE1, PGE2 and LTC4 sensitized uterine strips obtained from OVED rats to the effects of INS. The possible importance of PGE1 in improving uterine glucose metabolism in diabetic animals is discussed.     

Reduction of neutrophil influx diminishes lung injury and mortality following phosgene inhalation.

Phosgene inhalation causes a severe noncardiogenic pulmonary edema characterized by an influx of neutrophils into the lung. To study the role of neutrophils in lung injury and mortality after phosgene, we investigated the effects of leukocyte depletion with cyclophosphamide, inhibiting the generation of the chemotaxin leukotriene B4 with the 5-lipoxygenase inhibitor AA861 and impairing neutrophil migration with the microtubular poison colchicine. Cyclophosphamide, AA861, and colchicine injected before exposure significantly reduced percent neutrophils, protein, and thiobarbituric acid-reactive products in bronchoalveolar lavage fluid of rats exposed to phosgene (0.5 ppm X 60 min). Cyclophosphamide, AA861, and colchicine also significantly decreased mortality from phosgene (2.0 ppm X 90 min) in mice. Colchicine significantly reduced neutrophil influx, lung injury, and mortality even when given 30 min after phosgene exposure. We conclude that lung injury and mortality after phosgene exposure are associated with an influx of neutrophils into the lung. Prevention of neutrophil migration with colchicine may hold therapeutic potential in phosgene poisoning.     

The relationship between nitric oxide and leptin in the lung of rat with streptozotocin-induced diabetes

Lung structural changes and immunoreactivity of endothelial (eNOS)- and inducible nitric oxide synthase (iNOS) were investigated by light microscopy in lungs of treated and untreated diabetic rats. Diabetes was induced by a single intraperitoneal (i.p.) injection of 65 mg kg(-1) streptozotocin (STZ) in Wistar albino male rats. Diabetic rats received daily i.p. doses of dexamethasone (2 mg kg(-1)), leptin (0.5 microg kg(-1)) and intramuscular insulin (20 U kg(-1)) or a combination of these drugs for 1 week starting 4 weeks after the STZ injections. After treatment, the blood levels of glucose, leptin, insulin and nitrate/nitrite (NO(3) (-)/NO(2) (-)) were measured. Dilatation of alveoli and alveolar ducts, partial alveolar wall thickening and increased eNOS- and iNOS characterized the diabetic rat lungs. High blood glucose and nitrate/nitrite levels as well as low insulin and leptin levels were also present. Treatment with insulin, dexamethasone and a combination of these drugs resulted in improvement of the structural and immunohistochemical abnormalities. The most effective treatment was insulin therapy. Leptin administration resulted in increased relative amounts of extracellular material, which led to noticeable respiratory efficiency in the diabetic rat lungs. All treatments except leptin lowered blood glucose levels. The combination of insulin and dexamethasone increased blood leptin and insulin, while the remaining diabetic rats had blood with low leptin and insulin concentrations. These results suggest that therapy with insulin plus dexamethasone but not therapy with leptin is beneficial for diabetics.     

Inhibition of endogenous glucose production accounts for hypoglycemic effect of Spergularia purpurea in streptozotocin mice.

The purpose of this study was to determine the underlying mechanism of the hypoglycemic activity of the aqueous extract perfusion of Spergularia purpurea (SP) in diabetic mice and streptozotocin-induced diabetic rats. The aqueous extract was administered intravenously and the blood glucose levels were determined within 4 hours after starting the treatment. Plasma insulin concentrations and endogenous glucose production were also determined. The aqueous extract at a dose of 10 mg/kg produced a significant decrease in blood glucose levels in normal rats (P < 0.05), and even more in diabetic rats (P < 0.001). This hypoglycemic effect might be due to an extra-pancreatic action of the aqueous extract of SP, since the basal plasma insulin concentrations were unchanged after SP treatment. In diabetic mice, a similar effect was observed and the results showed that aqueous extract of SP caused a potent inhibitor effect on basal endogenous glucose production (p < 0.001). We conclude that aqueous extract perfusion of SP inhibits endogenous glucose production in mice. This inhibition is at least one mechanism explaining the observed hypoglycemic activity of this plant in diabetic animals.     

人脐带间充质干细胞移植对糖尿病大鼠血清学的影响

目的:观察人脐带间充质干细胞(hu MSCs)移植对糖尿病大鼠血糖、胰岛素和血清因子表达的影响。方法:随机选择12只Wistar大鼠通过腹腔注射链脲佐菌素50 mg/kg,血糖高于16.7 mmol/L者定为糖尿病大鼠,再将其随机分为糖尿病组和干细胞组,每组6只,同时选择6只雄性Wistar大鼠为正常组。干细胞组大鼠腹腔注射hu MSCs细胞悬液,糖尿病组注射PBS液。分别于注射2周、4周和6周后测定和比较各组大鼠的血糖、血清胰岛素、肿瘤坏死因子(TNF-α)和白介素-6(IL-6)的表达。结果:与正常组比较,糖尿病组和干细胞组大鼠的血糖水平均显著升高,胰岛素水平均显著降低(P0.01)。与糖尿病组比较,干细胞组大鼠注射hu MSCs后的血糖水平明显降低,胰岛素水平明显升高(P0.05),血清TNF-α和IL-6 m RNA水平均显著降低(P0.01)。结论:hu MSCs移植能显著降低糖尿病大鼠的血糖,促进其胰岛素分泌,同时降低血清TNF-α和IL-6的表达。     

金耳菌丝体多糖对实验性2型糖尿病大鼠的降血糖作用研究

本文研究了金耳菌丝体多糖(TMP)对实验性2型糖尿病大鼠血糖、血脂、胰岛素敏感性和抗氧化能力的影响。采用烟酰胺,链脲佐菌素和高脂饲料诱导2型糖尿病大鼠模型,以50和100mg/(kg.d)剂量的TMP连续灌胃48d,监测血糖,测定血清胰岛素、体重、脂代谢及抗氧化系统部分相关指标,并进行口服糖耐量实验。结果显示,TMP可明显降低2型糖尿病大鼠的血清葡萄糖、总胆固醇、甘油三酯和丙二醛水平,并极显著提高受试模型鼠的胰岛素敏感指数,血清超氧化物歧化酶活性和肝脏过氧化氢酶活性。此外,TMP能显著降低糖耐量实验中糖负荷后120min时糖尿病大鼠的血糖含量。上述结果表明TMP可有效降低实验性2型糖尿病大鼠的血糖水平,纠正脂代谢紊乱,改善胰岛素抵抗,增强抗氧化能力。