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1.
The feeding response following administration of the anti-metabolic glucose analogue, 2-deoxy-d-glucose (2DG), is conceptualized as an experimental model of glucoprivation, which may contribute to the understanding of inter-individual differences in glucose and carbohydrate intake and, ultimately, obesity. Although variation in the intake of several nutrients as well as food and water are known to be associated with genetic variation, it is not known whether 2DG-induced feeding is similarly genotype dependent. The present study therefore examined 2DG-induced feeding in mice of 11 inbred (A/J, AKR/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL6/J, C57BL10/J, DBA/2J, SJL/J, SWR/J, 129P3/J) and one outbred (CD-1) strains across a wide range of previously determined effective 2-DG doses (200, 400, 600, 800 mg/kg) and test times (1-4 h). Orderly dose-dependent increases in 2DG-induced feeding occurred after all four doses in outbred CD-1 and inbred DBA/2J mice, across the three highest doses for BALB/cJ, SJL/J and 129P3/J mice, and across the two highest doses for CBA/J and AKR/J mice. Limited instances of 2DG-induced feeding were noted only at the highest dose in A/J and C3H/HeJ mice, or at a moderate dose in C57BL/6J mice. Further, the full 2DG dose range failed to alter food intake in C57BL/10J mice, and produced significant reductions in food intake in SWR/J mice. Food intake after 2DG doses of 200-600 mg/kg, but not 800 mg/kg, displayed significant cross-correlation, suggesting that large 2DG doses may recruit non-specific effects upon food intake. There was no correlation between food intake in the absence (vehicle baseline) of and presence of 2DG, suggesting that the regulation of glucose intake in non-challenged mice does not predict subsequent responses to glucoprivic challenge. The data demonstrate genotype-dependent variability in this glucoprivic response, and may provide the basis for the subsequent identification of trait-relevant genes.  相似文献   

2.
The objective of this paper was to study the therapeutic effect of Stigma maydis polysaccharides in diabetic mice. Mouse models of types 1 and 2 diabetes were established. The body weight, food intake, water intake as well as blood sugar level and glucose tolerance of mice were measured. Stigma maydis polysaccharides can improve the symptoms of weight loss and polydipsia in diabetic mice, and had an obvious antagonistic effect on alloxan-induced hyperglycaemia. The glucose tolerance test also showed that the Stigma maydis polysaccharides had very good effects on suppression and prevention of acute hyperglycaemia. Stigma maydis polysaccharides have some improvement effect on alloxan-induced types 1 and 2 diabetes.  相似文献   

3.
The eating response that occurs following recovery from the effects of insulin or 2-deoxy-D-glucose (2DG) injection was examined in rats with hepatic vagotomy and/or coeliac ganglionectomy. Rats were deprived of food and injected with either saline (1 ml/kg), regular insulin (3 U/kg) or 2DG (200 mg/kg). Plasma glucose was measured periodically over the next 6 hr and then food was returned and intakes were measured over the next 2 hr. Rats increased food intake 6–8 hr after insulin or 2DG injection compared to the saline (control) condition. Nerve section did not affect the plasma glucose or food intake responses to insulin or 2DG injection. The results indicate that the innervation of the liver via the vagus nerve or coeliac ganglion is not involved in the delayed eating response to insulin and 2DG injection.  相似文献   

4.
The methanol extract of Gladiolus psittascinus bulb was evaluated for its antidiabetic activities in alloxan-induced diabetic rats. Blood glucose levels of the glucose loaded and alloxan-induced diabetic rats were estimated over 180 minutes using the O-toluidine and glucose-oxidase methods. The methanol extract at 1g/kg dose exhibited 16.2% decrease in blood glucose level in the glucose loaded rats and a peak effect of 78.9% in the alloxan-induced diabetic rats. The extract exhibited significant blood glucose lowering effects in the oral glucose tolerance test and type 2 diabetic rats. This study shows a possible beneficial effect of Gladiolus psittascinus in the management of non-insulin dependent diabetes (NIDDM).  相似文献   

5.
6.
Blood glucose and plasma insulin levels between C57BL/6J and ICR strain mice with nicotinamide (NA) and streptozotocin (STZ)-induced diabetes were compared to establish a suitable strain of the experimental diabetic mouse model. The mice were intraperitoneally treated twice with STZ (100 mg/kg) 15 min after injection of NA (120 mg/kg) at a 1-day interval, and non-fasting blood glucose level was then weekly monitored for 5 weeks. The blood glucose level in ICR mice gradually increased and was about 2-times higher than that in C57BL/6J mice at the end of the observation. The plasma insulin level in ICR mice was comparatively low, compared with that in C57BL/6J mice. ICR mice were also markedly glucose-intolerant when oral glucose tolerance test was performed. These results indicate that ICR strain is more sensitive than C57BL/6J strain as a mouse model with NA/STZ-induced mild diabetes.  相似文献   

7.
Changes in food induced by 2 deoxy-D-glucose (2 DG) have been investigated in newly lesioned rats during the two parts of the diurnal cycle. In a first experiment rats were injected with saline or 2 DG (250, 500, 750 mg/kg) at the beginning of the light or the dark period. In a second experiment rats were injected with saline or 2 DG (250 mg/kg) in the middle of the two periods after 0, 2, 4 or 6 hr of fasting. Results show that 2 DG exerts an inhibitory effect on food intake at night, as it does in intact rats, under ad lib conditions or after a short deprivation time. The stimulating effects of 2 DG on diurnal food intake observed in intact rats is not replicated in VMH rats. On the contrary an inhibition of intake follows a short food deprivation. The data suggest that 2 DG stimulates food intake only under metabolic and feeding conditions characteristic of the diurnal phase in intact rats. Since lipogenesis and hyperphagia are observed 24 hr a day in VMH animals, only inhibition could follow 2 DG.  相似文献   

8.
Helianthus annuus (sunflower) is an annual plant native to America that possesses a large inflorescence. The present study evaluated the acute toxicity, antidiabetic, oral glucose tolerance test (OGTT), and antioxidant effects of methanol extract of H. annuus leaves using alloxan-induced diabetic rats. The extract at the dose range of 300–3,600 mg/kg was tolerated by the rats. The extract (150, 300, and 600 mg/kg) showed a significant (p?p?>?0.05) differences between the extract-treated groups and glibenclamide (2 mg/kg)-treated groups. At 6 h posttreatment, there was a significant (p?p?>?0.05) difference in blood glucose level among the treatment groups. In diabetic OGTT, the blood glucose level of the extract (600 mg/kg)-treated group was significantly (p?p?>?0.05) difference between the extract- and glibenclamide (2 mg/kg)-treated groups. The extract produced a concentration-dependent increase in antioxidant activity. These findings suggest that H. annuus has potent antidiabetic and antioxidant activities and validate its folkloric use in traditional medicine for the treatment of diabetes mellitus.  相似文献   

9.
The new diagnostic criteria recommended by the American Diabetes Association (ADA) will only detect diabetic patients with fasting hyperglycemia, and leave patients with isolated post-challenge hyperglycemia (IPCH) and imparied glucose tolerance (IGT) unidentified. The WHO recommends that all those with abnormal fasting glucose should undergo the oral glucose tolerance test (OGTT) to exclude the diagnosis of diabetes (two-step strategy). This two-step strategy will leave out subjects with normal fasting glucose (<109 mg/dl). The aim of this study is to compare the WHO two-step strategy and the gold standard OGTT for all subjects. We re-analyzed the results of 907 high-risk patients who have been screened for diabetes mellitus and impaired glucose tolerance. All subjects were screened with an OGTT containing a 75-gram glucose load after fasting for 12 hours. The results were classified into three categories: the ADA criteria, the two-step strategy, and the OGTT. Using the ADA criteria, these 907 subjects can be classified has having normal fasting glucose (fasting plasma glucose - FPG < 109 mg/dl) in 715 subjects (78.9%), abnormal fasting glucose (FPG 110 - 125 mg/dl) in 107 subjects (11.8%), and diabetes mellitus (FPG > 126 mg/dl) in 85 subjects (9.4%). The WHO two-step strategy performed in 107 IFG subjects identified another 30 diabetic patients (FPG < 109 mg/dl and 2 hour post load > 200 mg/dl = IPCH) or 3.3%, and 49 patients with IGT, or 5.4% from all subjects. If the OGTT was performed on the 715 normal fasting glucose, it could identify another 40 diabetic patients or 4.4%, and another 178 IGT patients, or 19.6% of all subjects. This means that without OGTT to all subjects, 40 diabetic patients or 25.8% of all diabetic patients and 178 patients or 78.4% from all IGT subjects would have remained unidentified. From this study we can conclude that applying the WHO two-step strategy in subjects with IFG would fail to detect 25.8% of diabetic patients and 78.4% of IGT subjects. It is recommended that the old strategy of screening--the gold standard OGTT--should be used instead of the two-step strategy, at least in high-risk groups.  相似文献   

10.
Ficus glumosa Del (Moraceae) commonly called “African rock fig” is a large tree indigenous to southern part of Nigeria. Its stem bark has been of interest to researchers because of its use in the treatment of various disease conditions in Nigerian traditional medicine. The present study was aimed at evaluating the antidiabetic and antioxidant properties of the methanol extract of F. glumosa stem bark using alloxan-induced diabetic mice. The extract, at the dose of 62.5, 125, and 250?mg/kg showed a remarkable time-dependent decrease in blood glucose level in alloxan-induced diabetic mice. There was no significant difference between the extract-treated groups and the groups treated with 10?mg/kg distilled water and glibenclamide (2?mg/kg) respectively. At 6-h post-treatment, the blood glucose level for the groups treated with 62.5?mg/kg of F. glumosa and glibenclamide (2?mg/kg), respectively, were lower than the normal blood glucose level respectively for the groups before the induction of diabetes. F. glumosa showed its optimum antioxidant activity in DPPH spectrophotometric assay at the concentration of 100?μg/ml. The ferric reducing antioxidant power showed a significant concentration dependent increase in the total antioxidant power. These findings demonstrate that F. glumosa has both antidiabetic and antioxidant effects on experimental model of diabetes in mice and validate its use in Nigerian traditional medicine for the treatment of diabetes. Even in its crude form, the effects, especially at 62.5?mg/kg, were comparable to that of glibenclamide, an oral sulfonylurea with proven antidiabetic activity. This finding suggests that the extract could be a potential source of a novel antidiabetic and antioxidant agent for the treatment of diabetes mellitus.  相似文献   

11.
We examined the patient records of 6445 patient visits to an executive health surveillance program to evaluate the diagnostic yield from screening for diabetes mellitus by measurement of fasting serum glucose and hemoglobin A1c. We found increased fasting serum glucose levels (greater than or equal to 6.6 mmol/L) in 3% (197/6445), of whom only half received further confirmatory testing. Increased screening values for glucose were associated with a 70% incidence of diabetes mellitus and impaired glucose tolerance when subsequent oral glucose tolerance tests were performed. Confirmatory testing with the oral glucose tolerance test was equivalent in cost and superior in diagnostic yield to repeated fasting glucose determination. Nonetheless, preferential use by clinicians of repeated glucose determination was found to contribute to underdiagnosis. Hemoglobin A1c could not reliably predict impaired or diabetic glucose tolerance. We conclude that maximal value of screening for diabetes mellitus is achieved only by obligatory confirmatory oral glucose tolerance testing.  相似文献   

12.
In the present study interactions between analgesic effect of morphine with blockade of ATP-sensitive potassium channels and L-type calcium channels were investigated in alloxan-induced diabetic mice. A hot plate test was used to assess analgesic effect of drugs in adult male NMRI mice. All drugs were injected through an intraperitoneal route. A diabetic mouse model was established by injections of alloxan for three consecutive days. Seventy-two hours after the final injection, mice with a blood glucose level higher than 11.1mmol/l were considered as diabetic. The results showed that morphine at doses of 10 and 15mg/kg induced analgesia in both non-diabetic and diabetic mice, but the analgesic effect of morphine at dose of 7.5mg/kg was decreased in diabetic mice. Injections of an ATP-sensitive potassium channel blocker, glibenclamide (4, 8, 12, 20mg/kg) had no effect in non-diabetic mice, while at doses of 12 and 20mg/kg induced analgesia in diabetic mice. Blockade of L-type calcium channels with nimodipine at different doses (2.5, 5, 10 and 20mg/kg) was ineffective in non-diabetic mice, but at dose of 20mg/kg induced analgesia in diabetic mice. Co-administrations of glibenclamide (20mg/kg) or nimodipine (20mg/kg) along with different doses of morphine (5, 7.5 and 10mg/kg) improved the analgesic effect of the later drug in diabetic mice. According to the present results, it is possible that diabetes via affecting the potassium and calcium channels in the pain pathways may alter processing of pain in the peripheral and central nervous system.  相似文献   

13.
Deermice (Peromyscus maniculatus) did not increase their food intake above baseline following treatment with 2-deoxy-D-glucose (2DG, 500 or 1000 mg/kg). They did eat more following food deprivation or treatment with insulin at a high dose (100 U/kg). House mice (Mus musculus) showed hyperphagia to 2DG, low dose of insulin (5 U/kg) and deprivation.  相似文献   

14.
目的:探讨苦参碱对氧化型低密度脂蛋白(oxLDL)诱导的血管平滑肌细胞炎症反应及增殖凋亡的影响及分子机制。方法:oxLDL 处理人主动脉血管平滑肌细胞建立动脉粥样硬化模型。CCK-8 实验分析细胞活力和增殖。实时定量PCR(qRT-PCR)检测炎症因子白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)、IL-10 和IL-13 的mRNA 水平。流式细胞术分析细胞凋亡。蛋白印迹检测增殖标记蛋白细胞增殖核抗原-67(Ki-67)和增殖细胞核抗原(PCNA),细胞凋亡标记蛋白B 细胞淋巴瘤-2(Bcl-2) 和Bcl-2 相关蛋白X(Bax),信号转导及转录激活子3(STAT3)和信号转导及转录激活子5(STAT5)的表达。结果:与对照组相比,造模组促炎因子IL-1β和TNF-α的mRNA 水平大大提高,抗炎因子IL-10 和IL-13 mRNA 水平则显著降低(P<0.01)。与造模组相比,模型加药组促炎因子IL-1β和TNF-α的mRNA 水平显著降低,抗炎因子IL-10 和IL-13 的mRNA 水平明显升高(P<0.05)。造模组细胞增殖倍数和细胞凋亡率明显高于对照组,模型加药组细胞增殖倍数和细胞凋亡率明显低于造模组(P<0.05)。与对照组相比,造模组Ki-67、PCNA 和Bax 的表达显著升高,Bcl-2 显著降低(P<0.01)。与造模组相比,模型加药组Ki-67、PCNA 和Bax 的表达明显减少,Bcl-2 表达明显增多(P<0.05)。造模组p-STAT3 和p-STAT5 相对蛋白表达量显著高于对照组(P<0.01)。模型加药组p-STAT3 和p-STAT5 相对蛋白表达量明显低于造模组(P<0.05)。与造模组相比,模型加药组和模型+Ruxolitinib 组Ki-67、PCNA 和Bax 的表达明显减少,Bcl-2 表达明显增多(P<0.05);模型加药+Ruxolitinib 组Ki-67、PCNA 和Bax 的表达显著减少,Bcl-2 表达显著增多(P <0.01)。与造模组相比,模型加药组和模型+Ruxolitinib 组及模型加药+Ruxolitinib 组IL-1β和TNF-α的mRNA 水平都明显降低,IL-10 和IL-13 的mRNA 水平都明显升高(P<0.05)。结论:苦参碱可通过抑制JAK/ STAT3 通路的活化起到抗炎和抑制血管平滑肌细胞增殖和凋亡的作用。  相似文献   

15.
The aim of this work was to investigate the effect of daily oral administration of root bark methylene chloride/methanol extract of Ceiba pentandra (Linn) in streptozotocin-induced type-2 diabetic rats, and the effect of this treatment on the physiological and metabolic parameters that are related in diabetic animals. The diabetic rats were separated into four groups and each given the following samples by gavage, daily for 28 days: vehicle (diabetic control), Ceiba pentandra extract at the dose of 40 mg/kg, Ceiba pentandra extract at the dose of 75 mg/kg and glibenclamide (5 mg/kg). All the parameters were also determined in healthy (non diabetic) rats for comparison. The methylene chloride/methanol extract of Ceiba pentandra treatment significantly reduced the intake of both food and water as well as the levels of blood glucose, serum cholesterol, triglyceride, creatinine and urea, in comparison with diabetic controls. The treatment also improves impaired glucose tolerance but no effect was observed in the level of hepatic glycogen. The effect of Ceiba pentandra (40 mg/kg) was more prominent when compared to glibenclamide in lowering blood glucose, with the added benefit of considerably reducing serum cholesterol and triglyceride concentrations. The results of this experimental animal study indicated that Ceiba pentandra possesses antidiabetic activity; and thus is capable of ameliorating hyperglycaemia in streptozotocin-induced type-2 diabetic rats and is a potential source for isolation of new orally active agent(s) for anti-diabetic therapy.  相似文献   

16.
Bridelia micrantha (Hochst) Baill. (Euphorbiaceae), commonly known in English as “coast gold leaf” or “ogaofia” (the boss of the bush) in Igbo, is a semi-deciduous to deciduous tree up to 20?m tall with a dense rounded crown and tall, and bare stem indigenous to southern part of Nigeria. Its stem bark, which is yellow grey and smooth to slightly rough, has been of interest to researchers because of its use in the treatment of various disease conditions in Nigerian traditional medicine. The present study was targeted at investigating the antidiabetic and antioxidant effects of the methanol extract of B. micrantha leaves using alloxan-induced diabetic mice in vivo and in vitro. The extract, at the dose of 250, 500, and 1,500?mg/kg, showed a remarkable time-dependent decrease in blood glucose level in alloxan-induced diabetic mice. There was no significant difference between the extract-treated groups and the groups treated with 10?mg/kg distilled water and glibenclamide (2?mg/kg), respectively. Six hours posttreatment, the blood glucose level for the groups treated with 250?mg/kg of B. micrantha and glibenclamide (2?mg/kg), respectively, were lower than the normal blood glucose level respectively for the groups before the induction of diabetes. B. micrantha showed its optimum antioxidant activity in DPPH spectrophotometric assay at the concentration of 400?μg/ml. The ferric reducing antioxidant power showed a significant concentration-dependent increase in the total antioxidant power. These findings demonstrate that B. micrantha has both antidiabetic and antioxidant effects on experimental model of diabetes in mice and validate its use in Nigerian traditional medicine for the treatment of diabetes. Even in its crude form, the effects were comparable to that of glibenclamide, an oral sulfonylurea with proven antidiabetic activity. This finding suggests that the extract could be a potential source of a novel antidiabetic and antioxidant agent for the management of diabetes mellitus.  相似文献   

17.
Newly synthesized vanadyl-poly(gamma-glutamic acid) complex (VO-gamma-PGA) with a VO(O4) coordination mode was found to have potent antidiabetic activity in streptozotocin (STZ)-induced type 1 diabetic mice (STZ-mice), compared with that of a solution containing only vanadyl sulfate, VOSO4. This was the first example of orally active vanadyl complex of gamma-PGA for treating STZ-mice. To better define its efficacy, we examined here the effects of VO-gamma-PGA treatment in STZ-mice by oral administration at the dose of 10 mg V/kg body mass for a longer period time than our previous study. The improvement in diabetic states in STZ-mice compared with saline-treated nondiabetic normal Std ddY mice. It was found that the elevated blood glucose levels in STZ-mice significantly decreased after 3 days and sustained the normalized blood glucose level around 180-200 mg/dL (10-11.1 mM) for the last 14 days, which is close to the blood glucose levels 100-200 mg/dL (5.6-11.1 mM) in nondiabetic normal Std ddY mice. The improvement in diabetes was strongly corelated by the improvement in oral glucose tolerance ability, glycosylated hemoglobin (HbA1c) levels and blood pressure, and serum parameters. The present results confirmed that VO-gamma-PGA complex is a promising, orally active insulin-mimetic agent to treat type 1 diabetic mice.  相似文献   

18.
Thirty-six rats were injected IP with 2DG (0, 250, or 500 mg/kg) at 7-day intervals, once at light onset (7 a.m.) and once at dark onset (7 p.m.), and postinjection food intake was monitored for 24 hours. Five hundred mg/kg 2DG caused food intake to rise above control levels during the first 6 hours of daylight, regardless of whether the injection had occurred that morning or the previous evening, whereas intake during the first 6 hours of darkness was consistently below control levels. In a second study, 24 rats were injected first at 7 a.m. (500 mg/kg 2DG or saline), and 7 days later at 7 p.m. (opposite drug), and food was withheld 12 hours until the light:dark period had changed. For 12 hours after food was returned, 2DG again decreased nighttime food intake (Injection 1) and increased daytime intake (Injection 2). 2DG's dual long-term effects cannot be accounted for either by malaise or by an initial action that later is compensated by its opposite. Rather, 2DG (500 mg/kg) appears to exert two independent, opposite alimentary effects which persist 18-24 hours and which change direction with phase changes in the light:dark cycle.  相似文献   

19.
Ficus racemosa (Moraceae family) is used in traditional system of medicine for the treatment of several disorders including diabetes mellitus. The aim of the study was to investigate the antihyperglycemic and hypolipidemic activities of ethanolic extract of Ficus racemosa bark (FrEBet) in alloxan-induced diabetic rats. A total number of 30 animals were divided into 5 groups of six each. Diabetes mellitus was induced by single intraperitoneal injection of freshly prepared solution of alloxan monohydrate (150 mg/kg bw) dissolved in physiological saline in overnight fasted wistar rats. Dose dependent studies for FrEBet (100–500mg/kg bw) was carried out to find out the effective pharmacological dose (antidiabetic and hypolipidemic) to alloxan-induced diabetic rats. Blood glucose, plasma insulin, total cholesterol, phospholipids, triglycerides, free fatty acids, HDL cholesterol and LDL cholesterol levels in plasma, erythrocyte membranes, liver and kidney were determined by specific colorimetric methods. An increase in blood glucose was accompanied by an increase in total cholesterol, phospholipids, triglycerides, FFA and decrease in HDL choleterol in diabetic rats. Oral administration of FrEBet (300mg/kg bw) to diabetic rats restrored the status of blood glucose, lipids and lipoproteins to near normal range. Our investigation thus shows that FrEBet has potent antidiabetic and hypolipidemic effects in alloxan-induced diabetic rats and these effects were much comparable to that of the standard reference drug, glibenclamide.  相似文献   

20.
The present study was carried out to investigate the hypoglycaemic effects of metformin and garlic (Allium sativum Linn) in alloxan-induced diabetic dogs. The anti-diabetic activity of garlic had never been investigated in experimental diabetic dogs. Twenty-one adult dogs were randomly allocated into three equal groups consisting of seven dogs. The first group was the diabetic control, the second was the metformin treated and the third was the garlic-treated group. This study aimed to test 14-day oral administration of garlic (100 mg/kg) for its effects in alloxan-induced diabetic dogs in comparison with metformin (1,700 mg/dog/day) anti-diabetic activity. The mean decrease in blood glucose was 9.27 mg/dl for metformin and 25.93 mg/dl for garlic. The results showed that treatment with metformin non-significantly reduced blood glucose level (p?>?0.05) and significantly increased serum insulin level in diabetic dogs (p?<?0.05). In contrast to metformin, garlic resulted in a significant decrease in the level of blood glucose, with a concomitant significant increase in the serum insulin level in diabetic dogs (p?<?0.05). Garlic had a mild but significant blood glucose-lowering effect and the long-term use of this agent may be advantageous, over chemical drugs, in alleviating some of the chronic diseases and complications caused by diabetes.  相似文献   

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