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1.
In order to examine the involvement of insulin in the activity of Na+/glucose cotransporter in rat small intestine, we compared Na(+)-dependent uptake of D-glucose by brush-border membrane vesicles prepared from control, streptozotocin-induced diabetic, insulin-treated diabetic and starved diabetic rats. In four groups, the uptake of D-glucose showed a transient overshoot in the presence of Na+ gradient between medium and vesicles (medium greater than vesicles). The overshoot magnitude was increased (1.8-fold of controls) in diabetic brush border membrane vesicles and recovered to the control level by the treatment of diabetic rats with insulin. In contrast, increased uptake of D-glucose in diabetic rats was not recovered by the starvation of diabetic rats although the blood glucose level was the same as that of controls. Furthermore, we attempted to examine phlorizin binding activities among four groups. Scatchard analysis indicated that phlorizin binding to diabetic brush border membrane vesicles was increased (1.6-fold of controls) without a change of the affinity for phlorizin as compared with controls. Increased binding of phlorizin to diabetic brush border membrane vesicles was also recovered to the control level by the treatment of diabetic rats with insulin, but not by starvation. These results suggested that the increased activity of Na+/glucose cotransporter in diabetic rats was due to the increase of the number of cotransporter and that intestinal cotransporter was physiologically controlled by insulin, but not by blood glucose levels.  相似文献   

2.
Oral administration of Lactobacillus casei reportedly reduces blood glucose concentrations in a non-insulin-dependent diabetic KK-Ay mouse model. In order to determine if other lactobacillus strains affect glucose metabolism, we evaluated the effect of the probiotic strain Lactobacillus johnsonii La1 (LJLa1) strain on glucose metabolism in rats. Oral administration of LJLa1 via drinking water for 2 weeks inhibited the hyperglycemia induced by intracranial injection of 2-deoxy-D-glucose (2DG). We found that the hyperglucagonemic response induced by 2DG was also suppressed by LJLa1. Oral administration of LJLa1 for 2 weeks also reduced the elevation of blood glucose and glucagon levels after an oral glucose load in streptozotocin-diabetic rats. In addition, we recently observed that intraduodenal injection of LJLa1 reduced renal sympathetic nerve activity and enhanced gastric vagal nerve activity, suggesting that LJLa1 might affect glucose metabolism by changing autonomic nerve activity. Therefore, we evaluated the effect of intraduodenal administration of LJLa1 on adrenal sympathetic nerve activity (ASNA) in urethane-anesthetized rats, since the autonomic nervous system, including the adrenal sympathetic nerve, may be implicated in the control of the blood glucose levels. Indeed, we found that ASNA was suppressed by intraduodenal administration of LJLa1, suggesting that LJLa1 might improve glucose tolerance by reducing glucagon secretion via alteration of autonomic nerve activities.  相似文献   

3.
The effect of atorvastatin (Lipitor) on diabetes-induced changes in plasma lipids, oxidative stress and the ability of aortic tissues to generate prostacyclin was studied in streptozotocin diabetic rats. In diabetic rats, plasma total cholesterol, triglycerides and serum glucose significantly increased compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not affect hyperglycemia but significantly reduced plasma total cholesterol and triglycerides compared to diabetic rats. The oxidative stress markers urinary isoprostane, liver thiobarbituric acid reactive substances (TBARS) and plasma protein carbonyl content significantly increased in diabetic rats compared to nondiabetic rats. Atorvastatin admnistration to diabetic rats significantly reduced oxidative stress levels compared to diabetic rats, but urinary isoprostane and liver TBARS remained significantly higher than nondiabetic rats. Prostacyclin (PGI(2)) generation by aortic tissues significantly decreased in diabetic rats compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not reverse that inhibition. These results were discussed in the light of the possible effects of hyperglycemia and statins on NAD(P)H-oxidase and cyclooxygenase-2 activities and the genetic difference between rats and other mammals regarding the level of vascular superoxide dismutase (SOD) activity.  相似文献   

4.
Hon-Chi was used for anti-hyperglycemic activity screening in streptozotocin-induced diabetic rats (STZ-diabetic rats) in an attempt to develop new substances for handling diabetes. Mandarin Hon-Chi is red yeast rice fermented with Monascus pilous and Monascus purpureus. Single oral administration of Hon-Chi decreased plasma glucose in STZ-diabetic rats in a dose-dependent manner from 50 mg/kg to 350 mg/kg. Similar treatment with Hon-Chi also lowered the plasma glucose in normal rats as effectively as that produced in STZ-diabetic rats. In addition, oral administration of Hon-Chi at the highest dose (350 mg/kg) attenuated the elevation of plasma glucose induced by an intravenous glucose challenge test in normal rats. Moreover, mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) in liver from STZ-diabetic rats were reversed in a dose-dependent manner by the repeated oral treatment of Hon-Chi three times daily for two weeks. Otherwise, hyperphagia in STZ-diabetic rats was markedly reversed by similar repeated treatment of Hon-Chi. The obtained results suggest that oral administration of Hon-Chi could decrease hepatic gluconeogenesis to lower plasma glucose in diabetic rats lacking insulin.  相似文献   

5.
Cogent db, a compound herbal drug, was investigated for its possible antidiabetic effect in alloxan-induced diabetic rats. Oral administration of 0.15, 0.30 and 0.45 g/kg body wt. of the aqueous solution of Cogent db for 40 days exhibited a significant reduction in blood glucose, glycosylated haemoglobin and increased plasma insulin, total haemoglobin along with antihyperlipidemic effects in diabetic rats. The effective dose was found to be 0.45 g/kg body wt. It also prevents body weight loss in diabetic rats. An oral glucose tolerance test (OGTT) was also performed in experimental diabetic rats in which there was a significant improvement in glucose tolerance in rats treated with Cogent db. A comparison was made between the action of Cogent db and a known antidiabetic drug — glibenclamide (600 μg/kg body wt.). The antidiabetic effect of Cogent db was more effective than that observed with glibenclamide.  相似文献   

6.
Oral administration of carnitine in normal and diabetic subjects showed a marked decrease in the level of blood glucose during the oral glucose tolerance test (OGTT) except for the three hour samples in diabetic subjects, while a decrease in the level of subsequent blood pyruvate samples was observed during the OGTT in normal and diabetic subjects after the administration of carnitine. During the OGTT, the peak of blood glucose and blood pyruvate level was generally delayed in the diabetic subjects. Furthermore, the mean blood pyruvate levels were elevated above those of normal subjects during the late stages of the test. The mean levels of blood glucose and blood pyruvate of all samples after the administration of carnitine were significantly higher in diabetics than the corresponding values in noramls. Carnitine administration decreased the total blood amino acid nitrogen level only in diabetic subjects. Carnitine caused a highly significant increase in the activity of serum alanine aminotransferase in normal and diabetic subjects, while it had no effect on the activity of serum aspartate aminotransferase. In goats, the level of blood glucose during the intravenous glucose tolerance test (IVGTT) was not affected by carnitine (1,3 or 6 mg/kg body weight). Carnitine in all doses used had no effect on the total blood amino acid nitrogen during the IVGTT, or on the activity of serum alanine aminotransferase and serum aspartate aminotransferase in the fasting samples. Acetyl-D,L-beta-methylcholine had no effect on the level of blood glucose, total blood amino acid nitrogen, the activity of serum alanine aminotransferase or serum aspartate aminotransferase in normal and diabetic subjects. The level of blood pyruvate decreased both in normal and diabetic subjects, in the samples that represented the peak of the curve. Glycine betaine had no effect on blood glucose, pyruvate, total blood amino acid nitrogen and the activity of serum alanine aminotransferase or serum aspartate amino transferase in normal and diabetic subjects or in goats.  相似文献   

7.
Type 2 diabetes is quite diverse, including the improvement of insulin sensitivity by dipeptidylpeptidase-4 (DPP-4) inhibitor, α-glucosidase inhibitors, and the protection of β-cells islet. The aim of this study was to search the effect of trigonelline (Trig) on DPP-4, α-glucosidase and angiotensin converting enzyme (ACE) activities as well as β-cells architecture, and starch and glucose tolerance test. In surviving diabetic rats, the supplement of Trig potentially inhibited DPP-4 and α-glucosidase activities in both plasma and small intestine. The pancreas islet and less β-cells damage were observed after the administration of trig to diabetic rats. The increase of GLP-1 in surviving diabetic rats suppressed the increase of blood glucose level and improved results in the oral glucose and starch tolerance test. Trig also normalized key enzyme related to hypertension as ACE and improved the hemoglobin A1c and lipid profiles (plasma triglyceride, HDL-cholesterol, LDL-cholesterol, and total cholesterol), and liver indices toxicity. Therefore, these results revealed that Trig was successful in improving glycemic control, metabolic parameters, and liver function in diabetic rats. It is therefore suggested that Trig may be a potential agent for the treatment of type 2 diabetes.  相似文献   

8.
9.
ObjectiveOur aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance.ResultsHealthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin, in patients.  相似文献   

10.
11.
A previous study in our laboratory showed that streptozotocin (STZ) induced diabetic, deoxycorticosterone acetate (DOCA) induced hypertensive rats exhibited significantly lower levels of plasma glucose than did normotensive diabetic animals. The present experiments further investigate the effects of DOCA treatment on fasting levels of plasma glucose and insulin and on their changes after oral glucose challenge in nondiabetic and STZ-diabetic rats. It was found that, in nondiabetic rats, DOCA-induced hypertension was associated with normal glucose levels and glucose tolerance but with significantly lower levels of plasma insulin. DOCA-treated diabetic animals showed significantly lower levels of plasma glucose, but their plasma insulin concentrations were not significantly different from those of the DOCA vehicle treated diabetic rats. DOCA-treated diabetic rats also had significantly higher plasma levels of cholesterol and triglycerides. It is suggested that DOCA may have a direct or indirect action on the assimilation, production, or utilization of glucose, perhaps leading to an improvement in insulin sensitivity and subsequently a decrease in insulin secretion.  相似文献   

12.
目的:研究糖尿病并发抑郁症大鼠海马血脑屏障结构关键蛋白紧密连接蛋白(ZO-1)、基底膜蛋白(CoIV)、周细胞蛋白(a-SMA)的表达情况及其损伤机制。方法:采用高脂灌胃14 d后,再尾静脉注射链脲佐菌素(STZ,38mg/kg),随机分为2组(n=15):糖尿病组和糖尿病并发抑郁症组;正常大鼠随机分为2组(n=15):空白对照组和抑郁症组。糖尿病组与空白对照组正常饲养,糖尿病并发抑郁症组和抑郁症组慢性不可预知性应激28 d。检测各组大鼠血糖值的变化,Open-field及Morris实验评价大鼠行为学变化,透射电子显微镜观察大鼠海马血脑屏障形态学改变,免疫组化法检测大鼠海马血脑屏障关键蛋白ZO-1、CoIV、a-SMA表达情况。结果:与空白对照组比较,糖尿病并发抑郁症组大鼠血糖异常升高,自主活动次数减少,逃避潜伏期延长,空间探索时间减少(P < 0.05,P < 0. 01);海马血脑屏障内皮模糊,毛细血管管腔狭窄,周边胶质细胞终足水肿,ZO-1、α-SMA表达显著减少(P < 0. 05),CoIV的表达显著增加(P < 0.05);与糖尿病组比较,糖尿病并发抑郁症组大鼠自主活动次数显著减少(P < 0. 01),逃避潜伏期延长(P < 0.05),海马血脑屏障毛细血管管腔更为狭窄、胶质细胞终足水肿更为明显,a-SMA表达显著下降(P< 0.05)。结论:糖尿病并发抑郁症血脑屏障关键蛋白ZO-1、CoIV、α-SMA表达紊乱可能是其结构损伤发生机制之一。  相似文献   

13.
Several studies have reported that pulsed magnetic fields (PMFs) can be a choice of therapy for diabetic peripheral neuropathy. However, the exact underlying mechanism of PMF is still not known. The purpose of this study was, therefore, to investigate the effects of clodronate encapsulated with liposome, a specific agent depleting macrophage, on PMF-treated streptozotocin-induced type I diabetic rats with peripheral neuropathy. Effects of PMF, liposome-encapsulated clodronate (LEC) or their combined treatments were investigated in diabetic rats by measuring the thermal latencies, mechanical thresholds, whole blood glucose levels, serum insulin level, and body mass. In diabetic rats, PMF exhibited a decrease in the blood glucose levels but did not change the serum insulin level. Both mechanical thresholds and thermal latencies of diabetic rats enhanced throughout the PMF treatment. During the PMF treatment, the administration of LEC suppressed the PMF-induced decrease in blood glucose level, PMF-induced increase in mechanical threshold and thermal latencies in diabetic animals. In addition, PMF reduced the LEC-induced increase in insulin levels of diabetic rats. Findings demonstrated that although effects of both PMF alone and LEC alone on diabetic animals are mostly positive, LEC may remove the therapeutic efficacies of PMF in combined treatment.  相似文献   

14.
Chang SL  Lin KJ  Lin RT  Hung PH  Lin JG  Cheng JT 《Life sciences》2006,79(10):967-971
In this study, intravenous glucose tolerance test (ivGTT) and insulin challenge test (ICT) were applied to evaluate the influence of electroacupuncture (EA) on insulin sensitivity in rats. Firstly, hypoglycemic activity was confirmed on normal Wistar rats (36+/-12%) and streptozotocin (STZ)-induced diabetic rats (13+/-8%) after 60 min of 15 Hz EA on bilateral Zusanli acupoints. The rats were divided into the experiment group (EG) and control group (CG) randomly. After fasting, plasma glucose and insulin levels were assayed in the normal Wistar rats undergoing ivGTT. Plasma glucose levels and hypoglycemic activity were also evaluated in the normal Wistar rats and STZ diabetic rats during ICT. As the data showed, EA improved the glucose tolerance from 15 to 90 min (p<0.005 compared with the plasma glucose levels of the CG) during ivGTT. In addition, significant improvement in the Homeostasis Model Assessment (HOMA) index was found in the EG from 15 to 90 min (p<0.005 compared with the CG). More hypoglycemic activity was achieved in normal Wistar and STZ diabetic rats in the EG than in the CG (from 30 to 60 min) during ICT. In conclusion, the results suggest that 15 Hz EA at bilateral Zusanli acupoints improved glucose tolerance. Thus, EA should be considered as an alternative method for improving insulin sensitivity and/or increase insulin-hypoglycemic activity in rats.  相似文献   

15.
The present work examined the effect of chronic oral administration of quercetin, a flavonoid antioxidant, on blood glucose, vascular function and oxidative stress in STZ-induced diabetic rats. Male Wistar-Kyoto (WKY) rats were randomized into euglycemic, untreated diabetic, vehicle (1% w/v methylcellulose)-treated diabetic, which served as control, or quercetin (10mgkg(-1) body weight)-treated diabetic groups and treated orally for 6 weeks. Quercetin treatment reduced blood glucose level in diabetic rats. Impaired relaxations to endothelium-dependent vasodilator acetylcholine (ACh) and enhanced vasoconstriction responses to alpha(1)-adrenoceptor agonist phenylephrine (PE) in diabetic rat aortic rings were restored to euglycemic levels by quercetin treatment. Pretreatment with N(omega)-nitro-l-arginine methyl ester (l-NAME, 10microM) or methylene blue (10microM) completely blocked but indomethacin (10microM) did not affect relaxations to ACh in aortic rings from vehicle- or quercetin-treated diabetic rats. PE-induced vasoconstriction with an essentially similar magnitude in vehicle- or quercetin-treated diabetic rat aortic rings pretreated with l-NAME (10microM) plus indomethacin (10microM). Quercetin treatment reduced plasma malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HNE) content as well as increased superoxide dismutase activity and total antioxidant capacity in diabetic rats. From the present study, it can be concluded that quercetin administration to diabetic rats restores vascular function, probably through enhancement in the bioavailability of endothelium-derived nitric oxide coupled to reduced blood glucose level and oxidative stress.  相似文献   

16.
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。  相似文献   

17.
OBJECTIVE--To examine the traditional view that unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation in insulin dependent diabetes mellitus are manifestations of autonomic neuropathy. DESIGN--Perspective assessment of unawareness of hypoglycaemia and detailed assessment of autonomic neuropathy in patients with insulin dependent diabetes according to the adequacy of their hypoglycaemic counterregulation. SETTING--One routine diabetic unit in a university teaching hospital. PATIENTS--23 Patients aged 21-52 with insulin dependent diabetes mellitus (seven with symptoms suggesting autonomic neuropathy, nine with a serious clinical problem with hypoglycaemia, and seven without symptoms of autonomic neuropathy and without problems with hypoglycaemia) and 10 controls with a similar age distribution, without a personal or family history of diabetes. MAIN OUTCOME MEASURES--Presence of autonomic neuropathy as assessed with a test of the longest sympathetic fibres (acetylcholine sweatspot test), a pupil test, and a battery of seven cardiovascular autonomic function tests; adequacy of hypoglycaemic glucose counterregulation during a 40 mU/kg/h insulin infusion test; history of unawareness of hypoglycaemia; and response of plasma pancreatic polypeptide during hypoglycaemia, which depends on an intact and responding autonomic innervation of the pancreas. RESULTS--There was little evidence of autonomic neuropathy in either the 12 diabetic patients with a history of unawareness of hypoglycaemia or the seven patients with inadequate hypoglycaemic counterregulation. By contrast, in all seven patients with clear evidence of autonomic neuropathy there was no history of unawareness of hypoglycaemia and in six out of seven there was adequate hypoglycaemic counterregulation. Unawareness of hypoglycaemia and inadequate hypoglycaemic counterregulation were significantly associated (p less than 0.01). The response of plasma pancreatic polypeptide in the diabetic patients with adequate counterregulation but without autonomic neuropathy was not significantly different from that of the controls (change in plasma pancreatic polypeptide 226.8 v 414 pmol/l). The patients with autonomic neuropathy had a negligible plasma pancreatic polypeptide response (3.7 pmol/l), but this response was also blunted in the patients with inadequate hypoglycaemic counterregulation (72.4 pmol/l) compared with that of the controls (p less than 0.05). CONCLUSIONS--Unawareness of hypoglycaemia and inadequate glucose counterregulation during hypoglycaemia are related to each other but are not due to autonomic neuropathy. The blunted plasma pancreatic polypeptide responses of the patients with inadequate hypoglycaemic counterregulation may reflect diminished autonomic activity consequent upon reduced responsiveness of a central glucoregulatory centre, rather than classical autonomic neuropathy.  相似文献   

18.
Various 3,4,5-triarylpyrroles were synthesized and evaluated for their in vivo antihyperglycemic activity in sucrose-loaded (SLM) and/or streptozotocin-induced (STZ) diabetic rat models. Three of the test compounds, 2-methyl-4,5-diphenyl-3-substituted-phenyl-1H-pyrroles (3c, d and h) showed significant inhibition on postprandial hyperglycemia in normal rats post sucrose loaded. These compounds also showed lowering of plasma glucose level in STZ-induced diabetic rat model.  相似文献   

19.
This study determined whether exercise training in rats would prevent the accumulation of lipids and depressed glucose utilization found in hearts from diabetic rats. Diabetes was induced by intravenous streptozotocin (60 mg/kg). Trained diabetic rats were run on a treadmill for 60 min, 27 m/min, 10% grade, 6 days/wk for 10 wk. Training of diabetic rats had no effect on glycemic control but decreased plasma lipids. In vivo myocardial long-chain acylcarnitine, acyl-CoA, and high-energy phosphate levels were similar in sedentary control, sedentary diabetic, and trained diabetic groups. The levels of myocardial triacylglycerol were similar in sedentary control and diabetic rats but decreased in trained diabetic rats. Hearts were perfused with buffer containing diabetic concentrations of glucose (22 mM) and palmitate (1.2 mM). D-[U-14C] glucose oxidation rates (14CO2 production) were depressed in hearts from sedentary diabetic rats relative to sedentary control rats. Hearts from trained diabetic rats exhibited increased glucose oxidation relative to those of sedentary diabetic rats, but this improvement was below that of the sedentary control rats. [9,10(-3)H]palmitate oxidation rates (3H2O production) were identical in all three groups. These findings suggest that exercise training resulted in a partial normalization of myocardial glucose utilization in diabetic rats.  相似文献   

20.
Kim HJ  Kong MK  Kim YC 《BMB reports》2008,41(10):710-715
This study investigated the effect of Phellodendri Cortex extract on hyperglycemia and diabetic nephropathy in streptozotocin-induced diabetic rats. Male Sprague-Dawley rats were divided into normal control (NC), diabetic control (DC), and diabetic treatment with Phellodendri Cortex extract (DP). Over a 4-week experimental period, Phellodendri Cortex extract was administered orally at 379 mg/kg BW/day. The final fasting serum glucose level, urine total protein level, and relative left kidney weight in the DP group were significantly lower than the DC group. Renal XO and SOD activities in the DP group were significantly lower than the DC group and renal CAT activity in the DP group was significantly higher than the DC group. Tubular epithelial change was reduced in the DP group compared to the DC group. These results indicated that Phellodendri Cortex can reduce glucose level and prevent or retard the development of diabetic nephropathy in streptozotocin-induced diabetic rats.  相似文献   

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