AIM To obserwe tb e effect of pentagastrin (G-5) on IL-1β induced inhibition of insulin secretion in newbornrat islet of Langerhans.METHODS Islets of Langerhans of 3- to 5-day-old rats were isolated by collagenase digestion. The isletswere maintained free-floating in culture medium RPMI-1640, containing 10% (V/V) calf serum, anddistributed randomly in 96-well plastic plates (6 wells in each group). There are 15 islets per well in 0.2 mLculture medium. The islets were kept at 37℃ in mixed gases of 5% CO2 and 95% humidified air for the timerequired by the experimental design. Three experiments were performed in this study. (①) IL-13 inducedinhibition of insulin secretion in isolated islets of Langerhans. (②) Effect of G-5 on IL-lβ induced inhibition ofinsulin secretion. ③ Effect of G-5 on the functional repair of islet B-cells inhibited by IL-1β. Accumulatedand glucose stimulated insulin secretion was measured by radioimmunoassay in all studies. Data are presentedas ~ ± s. Differences between groups were analyzed using the Student's t test. P <0.05 was consideredsignificant.RESULTS The function of islet B-cells, which has been received 1L-1β treated for 24 hours, was dose-dependently inhibited. The accumulated and glucose stimulated insulin secretion was significantly lower thanthat of the control group (P<0. 05). The inhibitory effect of IL-1β on islet B-cells can be partially reversedby G-5. Accumulated and stimulated insulin secretion of G-5 0.6 ng/mL and 0.8 ng/mL groups wassignificantly higher than that of IL-1β treated alone group (P<0.05). The function of islet B-cells, whichreceived IL-iβ treatment for 24 hours, could partially recover after G-5 treatment for another 24 hours. Butaccumulated and glucose-stimulated insulin secretion in groups with G-5 treatment for 10 hours groups had nosignificant difference as compared with IL-1β treated alone group (P>0.05).CONCLUSION The present results indicate that G-5 may have a protective effect against the toxicity of IL-1β on islet B-cells.

Antioxidant activity of curcumine as protector on methylmercury induced pancreas damage in mice

Curcumin has been reported to have a strong antioxidant activity.In recent years,use of antioxidant in reducing heavy metal toxicities has been increased worldwide.In this study,we investigated the protective effects of curcumin on methylmercuryinduced pancreas damage in mice.Briefly,50 male mice were divided into five groups as follows:negative control (mice were given daily with aquadest);positive control (mice were orally given 2 mg/kg BW methylmercury daily for 35 d);and the treatment groups (mice were orally adminstered with curcumin 100 mg;200 mg;400 mg/kg BW daily for 35 d,and from 5th day,animals were given 2 mg/kg BW methylmercury daily 1 h after curcumin administration for 30 d).On day 35,levels of glucose,insulin,MDA,SOD and GPx were measured.Pancreas also was fixed in 10％ neutral buffered formalin solution for histopathological examination.The results revealed that methylmercury toxicity induced a significant increase in the levels of glucose and MDA.Moreover,a significant decrease in insulin,SOD and GPx levels was observed,and pancreas tissues showed degeneration and necrotic changes in the islets of Langerhans.Treatment with curcumin (400 mg/kg BW but not 200 mg/kg BW and 100 mg/kg BW) significantly (P＜0.05) decreased glucose and MDA levels in pancreas in mercury-induced mice.Treatment with curcumin 400 mg/kg BW also significantly increased insulin,SOD and GPx levels and reversed the histopathological damage in methylmercury-induced mice.Taken together,curcumin could be a potent natural herbal product,which had pancreas protective effect against methylmercury-induced pancreas damage in mice.

Objective To sludy the relationship between advanced glycosylation end products (AGE) and protein kinase C (PKC), and their effects on ranal alteration in diabetic rats.Methods Insulin or anlinoguanidine was administered to diabetic rats. Blood glucose, hermoglobin A1c (HbA1c ), glomemlar tissue extracts AGE ( GTEAGE ), PKC, glomerular basement membrane thickness ( GBMT ) and udne protein/creatinine (Pr/Cr) ratio in diabetic rats were measured and analysed.Results LeveLs of blood glucose, HbA1C and AGE,PKC activity, the Pr/Or ratio and GBMT were all significantly increased ( p values all less than 0.01 ) in diabetic rats. Insulin could decrease the formation of kbAlc and AGE, and improve PKC activity.Aminoguanidine had no influecce on PKC activity (P>O.05) although it decreased the formation of AGE. Botah drugs could de4ay the increase of urine Pr/Cr ratio and GBMT ( P<0.05 or P< 0.01).Conclusions Chronic hyperglycemia may lead to an increase of PKC activity. HbAlc and AGE may not directly coritribute to alterations of PKC activity, but the increase of PKC activity could promote the action of AGE on GEM thickening. It is important to inhibit the formanion of AGE and reduce the PKC activity so as to pceveat or delay the development of diabetic nephropathy.

多梗死性痴呆患者血浆、脑脊液胰岛素含量与智能水平的相关性研究

Objective To study the change of plasma and cerebrospinal fluid (CSF) insulin levels and the relationship to intellectual level in patients with multi infarct dementia (MID).Methods The concentration of insulin in plasma and CSF was determined by RIAs in 55 patients with MID. 72 patients with cerebral infarction(CI) and 32 normal subjects were used as controls. Mini mental state examination (MMSE) was used to examine the intellectual level of patients, with DSM IV diagnosis standard and Hachinski Ischemia Score as references. Results The patients in MID had significantly higher plasma insulin level than that in normal controls ( P < 0.01 ), but lower CSF insulin and reduced CSF to plasma insulin ratio (P< 0.01). There was a positively correlated between CSF to plasma insulin ratio and MMSE score for MID as a whole. The patients in CI acute phase group had a higher plasma insulin levels than that in normal controls ( P < 0.05 ) , but CSF to plasma insulin ratio differed statistically from either MID acute episode group or stationary phase group ( P < 0.01 ). Conclusion The change of plasma and CSF insulin levels may be one of the pathophysiological mechanisms that bring about intellectual level decline in MID. CSF to plasma insulin ratio may be used as a marker of intellectual level declining for patients with MID.

高效Pdx1/insulin双报告基因载体的构建及其初步应用

背景:胰岛细胞移植是治疗1型糖尿病有效的方法之一,然而移植细胞来源短缺限制了其临床应用.多能干细胞有望成为胰岛细胞移植的理想种子细胞,但其向胰岛β细胞分化是一个复杂的过程.目的:构建高效Pdx1/insulin双报告基因载体,探讨其实时监测诱导多能干细胞向胰岛β细胞分化中关键性基因表达的可行性.方法:首先在pTiger载体上引入嘌呤霉素抗性,然后以646 bp的小鼠Ins1启动子替换了原来载体上410 bp的小鼠Ins1启动子,获得高效Pdx1/insulin双报告基因载体.后,将载体导入INS-1细胞和诱导多能干细胞,验证其功能.结果与结论:①实验成功构建了高效Pdx1/insulin双报告基因载体;②在INS-1细胞中验证了载体获得嘌呤霉素抗性,提高了insulin表达效率,并在INS-1细胞中检测到Pdx1和insulin的表达;③实验初步证明了Pdx1/insulin双报告基因能够有效监测细胞分化过程中Pdx1和insulin基因的表达.

Basal insulin and GLP-1 receptor agonists:A complementary approach to achievement of glycemic control

Today,we are fortunate to have multiple therapeutic agents that address the pathophysiologic defects resulting in hyperglycemia in type 2 diabetes. Evidence from clinical trials,as well as experience in practice, support recent treatment guidelines which call for the early combination of agents with complementary mechanisms of action to help patients achieve and maintain individualized glycemic targets. In patients with type 2 diabetes not achieving adequate glycemic control despite the addition of basal insulin,one such combination that has been shown to be safe and effective in multiple clinical trials, is the combination of basal insulin and a glucagon-like peptide 1 receptor agonist(GLP-1 RA). Through complimentary mechanisms of action,this regimen improves glycemic control and does so with significantly less hypoglycemia and with favorable effects on body weight compared with the addition of rapid-acting insulin(e.g.,basal-bolus insulin regimen). The addition of a GLP-1 RA should therefore be considered in patients with type 2 diabetes suboptimally controlled with basal insulin.

多囊卵巢综合征患者IL-18的表达水平及其相关性研究

目的:检测白细胞介素18(IL-18)在多囊卵巢综合征(PCOS)患者表达水平,探讨其与胰岛素(Insulin)和胰岛素抵抗指数(HOMA-IR)的关系.方法:检测实验组与对照组患者的体重指数(BMI)、IL-18、胰岛素(Insulin)、空腹血糖(FBG)水平,并计算HOMA-IR.研究IL-18水平与BMI、Insulin、FBG及HOMA-IR的相关性.结果:实验组患者的BMI、血清IL-18、Insulin及HOMA-IR明显高于对照组(P＜0.05);实验组患者血清IL 18水平与Insulin、HOMA IR呈正相关(P＜0.05).结论:IL-18在PCOS患者中的水平明显升高,且与患者的Insulin水平、HOMA-IR呈正相关,IL-18在PCOS的发病过程中起到重要作用.

Effects of pomegranate ethyl acetate extract on rat islet cells

Objective The present study investigated the effects of pomegranate ethyl acetate extract (PEE) on cell viability of primary rat islet cells.Methods PEE was extracted by using 95％ ethanol and a series of organic solvents.Primary isolated islet cells of rat were cultured in high glucose and/or high fat conditions with or without PEE.Cell viability was determined by MTT assay.Insulin secretion was assessed by using radioimmunoassay.Results Insulin levels were significantly higher in cells treated with high glucose+PEE,palmitic acid+PEE,and olein acid+PEE compared to the cells treated with high glucose,palmitic acid,or oleic acid alone,in which the insulin levels were markedly less than that of the normal control group.Conclusion PEE promotes islet cell growth and insulin secretion,which is suggested that PEE can protect islet cell function in both high glucose and high fatty acid environments.