Objective To evaluate the effects of saxagliptin on β cell function of type 2 diabetic patients. Methods The Cochrane Library, PubMed, EMbase, CBM, VIP, and CNKI were searched from their establishment to November, 2011, for relevant randomized controlled trials on the effects of saxagliptin on β cell function in type 2 diabetic patients. Language was limited to Chinese and English only. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and evaluated and cross-checked the methodological quality. Then meta-analysis was conducted using RevMan 5.0 software. Results Five RCTs were included. The results of meta-analysis showed that: HOMA-B was significantly increased in the saxagliptin (or saxagliptin plus routine treatment) 2.5 mg, 5 mg, and 10 mg groups (MD=8.03, 95%CI 4.57 to 11.48, Plt;0.000 01; MD=7.50, 95%CI 4.27 to 10.73, Plt;0.000 01; MD=17.45, 95%CI 13.93 to 20.97, Plt;0.000 01); HOMA-IR was similar between saxagliptin 2.5 or 10 mg group, and control group (MD= –0.05, 95%CI –0.18 to 0.08, P=0.47; MD= –0.18, 95%CI –0.60 to 0.24, P=0.4). Conclusion Current evidence shows that saxagliptin is effective in improving β cell function and insulin resistance. Due to short follow-up and small sample size, this conclusion has to be further proved by more high-quality RCTs.
Objective To investigate the effect of short-term administration of growth hormone (GH) on serum insulin-like growth factor-1 (IGF-1) level and nutritional status in patients after gastrointestinal operation, and evaluate whether postoperative application of GH rise the risk of tumor recurrence. Methods Forty-eight patients undergoing major gastrointestinal operation were randomly divided into two groups: GH group （n=24） and control group （n=24）. The two groups received isocaloric isonitrogenous nutrition with daily injection of either GH 0.15 U/kg or placebo for a period of day 3-9 postoperatively. Serum albumin, fibronectin, and IGF-1 were measured before operation as a baseline, and day 3 and 10 after operation using standard laboratory techniques. Nitrogen balance was measured daily from day 3 to day 9 after operation. Postoperative complications and adverse reaction were observed. All cancer patients received regular abdominal B-type ultrasonography and chest X-ray examination during 2 years of follow-up. Results Compared with control group, GH treatment did not influence serum IGF-1 and serum albumin level （Pgt;0.05）, but improved significantly the rise from day 3 to day 10 of serum fibronectin level 〔(22.8±5.8) mg/L vs.（9.6±3.6） mg/L， P＜0.05〕 and the cumulative nitrogen balance 〔（11.37±16.82） g vs.（－9.11±17.52） g， P＜0.01〕 postoperatively. There was no severe adverse effects and complications during GH treatment. The tumor-recurrence rates were not statistically different between two groups during follow-up. Conclusions Short-term administration of low-dose GH combined with early nutrition support can improve total nitrogen retention and protein metabolism, but not influence serum IGF-1 level after major abdominal surgery. Short-term administration of low-dose GH may not cause the tumor-recurrence.
Objective To investigate the insulin receptor expression and binding characteristics of H22 rat hepatic cancer cell membrane with 125Iinsulin and the possibility of using insulin as a carrier for the receptor mediated targeted therapy. MethodsInsulin was radiolabelled using ChT method, isolated and purified by polyacrylamide gel electrophoresis, the labelled 125Iinsulin was measured by specific activity selfreplacement and over dose receptor combination experiment. The rat H22 hepatocarcinoma cells, normal rat hepatic cells were made, continuing the value Kd and Bmax of 125Iinsulin binding with insulin receptor on rat H22 hepatocarcinoma and normal hepatic cells membrane were evaluated in vitro, the competed binding curve was pictured. The binding Kd and Bmax value of 125Iinsulin receptor were evaluated with t test and receptor binding curve was tested with Scatchard method. ResultsThe Bmax value of rat H22 hepatocarcinoma cell receptor ［(5.6±1.1) pmol/106 cell］ was higher than that of normal hepatic cell ［(3.2±0.8) pmol/106 cell］ significantly (P＜0.05). The Kd value of H22 cell ［high and lowaffinity vs (1.8±0.6) nmol/L and (32.0±10.7) nmol/L］ and normal hepatic cell ［high and low affinity vs (2.1±0.9) nmol/L and (37.0±12.3) nmol/L］ were not significant respectively. In this experiment, it was specific when 125Iinsulin combined with receptor on H22 hepatocarcinoma cell and rat normal hepatic cell membrane. Conclusion This experiment showed that the receptor expresses much more significantly on H22 hepatocarcinoma cell membrane than that on normal rat hepatic cell membrane, 125Iinsulin combining with receptor on H22 hepatocarcinoma cell and rat hepatic cell membrane is highly specific. We may use insulin as an anticancer carrier to mediate insulin combined with receptor on hepatocarcinoma cell membrane in the target treatment of hepatic cancer.
ObjectiveTo explore the effect of endotoxin on insulin secretion from islet βcell of rat pancreas.MethodsAfter the model of endotoxemia was established in rats with intraperitoneal injection of LPS (2 mg/kg),the changes of insulin level in the serum and pancreas were dynamically determined, the expression of inducible nitric oxide synthase (iNOS) by situ hybridization and DNA damage in islet cells were also observed, the effect of sodium nitroprusside (exogenous NO) on synthesis and secretion of insulin from isolated islet βcell of normal rat pancreas under high glucose stimulation was also evaluated.ResultsThe level of glucose and insulin in plasma were significantly increased at 12th and 6th h, respectively and kept on 3 d after injection of LPS,but the insulin level in pancreas was not remarkably altered.The expression of iNOS and DNA damaged significantly enhanced at 6 d after endotoxemia. The high glucosestimulated insulin synthesis and secretion were bly inhibited by exogenous NO.ConclusionThese findings suggest that LPS be stimulate the expression of iNOS and NO product,which inhibites synthesis and secretion of insulin in islet βcells,but it stimulates insulin secretion by another mechanism,and results in dysfunction and destruction of the rat pancreas.
Diagnosis and surgical procedures were studied in this paper. Twentyfive cases of insulinoma were treated surgically from 1970 to 1997, in which 10 patients had Whipple′s triad so that the early diagnosis could be made. The sites of tumours were found in 10 out of 12 undergoing. Selective celiac angiongraphy with the accuracy rate of 83%, but B-ultrasonography and CT gave only 10% (4 out of 25) and 40%(8 out of 20) respectively. In this series, 5 cases underwent bodytail pancreatectomy and 20 cases enucleation of insulinoma. Blood glucose levels were tested during operation in 15 cases, and they all reached the normal level one hour after the tumours were completely removed. The authors consider that Whipple′s triad is the main basis in diagnosis of insulinoma. The selective celiac angiongraphy play an important role in detecting and locating the tumour. If diagnosis is made, surgical operation should be taken. The blood glucose monitoring during operation is the hallmark for complete resection of insulinomas.
Objection To investigate the changes of insulin and insulin receptor in asthma patients.Methods Forty asthma patients were allocated into two groups：20 newly diagnosed treatment–naiuml;ve mild-moderate asthma patients，20 mild-moderate persistent asthma patients treated with inhaled corticosteroid. 20 healthy volunteers were enrolled as normal control.Blood samples were obtained from 40 asthma patients and 20 healthy volunteers.Total and differential leukocyte counts,blood glucose concentration and serum insulin concentration were measured.The level of lymphocyte insulin receptor in peripheral blood were assayed by flow cytomertry.Pulmonary function were performed at the same time.Results The numbers of eosinophil in the two asthma groups were significantly higher than those in the normal control group [(4.04±2.57)% and (4.24±2.34)% vs (0.90±1.38)%，Plt;0.05)，the levels of insulin and insulin receptor in the treatment-naiuml;ve group were significantly higher than those in the control group [insulin：(13.00±5.20)mIU/L vs (10.08±3.79)mIU/L，Plt;0.05；insulin receptor：(2.59±3.11)% vs (0.99±0.62)%，Plt;0.05).Conclusion Insulin secretion and insulin receptor expression in asthma patients are increased in the presence of inflammation.
Objective To investigate the expressions of insulin like growth factor binding protein -3 （ IGFBP-3 ） in serum and bronchoalveolar lavagae fluids （ BALF ） of patients with non-small cell lung cancer ， and explore the clinical significance in dignosis and prognosis of lung cancer.Methods The bronchoalveolar lavagae fluids （ BALF ） were collected by bronchoscopy in 80 cases with non-small cell lung cancer and 14 healthy subjects.The expression of IGFBP-3 in serum and BALF were detected by immunoradioassay.Results The expression of IGFBP-3 in serum and BALF of lung cancer group were significantly lower than that of health group（Plt;0.05）.IGFBP-3 levels were significantly lower in those patients with lymphoid node metastasis or metastasis or TNMⅢ-TNMⅣ than those without metastasis or TNMⅠ-TNMⅡ（Plt;0.05）.In lung cancer group，the levels of the IGFBP-3 in serum and BALF had a significantly positive correlation（r=0.415，r=0.355，Plt;0.01）.Conclusion The IGFBP-3 may play an important role in the development of non-small cell lung cancer and is valuable in dignosis and prognosis of lung cancer.
Objective To investigate the protective effects of recombinant human insulin-like growth factor-1 ( rhIGF-1) on apoptosis of diaphragm in rats with COPD and its impact on pulmonary function. Methods Forty-five male Wistar rats were randomly divided into three groups, ie. a normal control group, a model group, and an IGF-1 intervention group, with 15 rats in each group. The rats in the model group and IGF-1 group were exposed to 5% smoke ( 30 min perday, lasting 28 days) in a sealed box, and 200 μg lipopolysaccharide was injected intratracheally on the 1st and 14th day. The rats in the IGF-1 group were given rhIGF-1 ( 60 μg /100 g) additionally by subcutaneous injection once a day, lasting 28 days. On the 1st, 14th, 28th day, 5 rats from each group were sacrificed. The weight, rate of apoptosis, Fas gene and Fas protein expression of isolated diaphragms were detected. The pulmonary function was measured on the 28th day before sacrificed. Results The mass of diaphragms, minute ventilation ( VE) , peak expiratory flow ( PEF) , inspiratory capacity ( IC) , forced expiratory volume in 0. 3 second ( FEV0. 3) of themodel groupand IGF-1 group were all decreased compared with the control group ( P lt; 0. 05) . The mass of diaphragms, VE, IC of the IGF-1 group were higher than those of the model group ( P lt;0. 05) , and the differences of PEF and FEV0. 3 were not significant ( P gt; 0. 05) . On the 14th, 28th day, rate of apoptosis, Fas gene and protein expressions in the IGF-1 group were lower than those in the model group, and still higher than those in the control group ( P lt; 0. 05) . Conclusions Fas/FasL mediated apoptosis way is involved in the diaphragm apoptosis. rhIGF-1 may reduce the apoptosis of the diaphragmand improve the VE and IC of rats with COPD by intervening Fas/FasL pathway.
【Abstract】 Objective To explore the new therapy for pulmonary fibrosis by observing the effects of insulin-like growth factor 1 ( IGF-1) treated mesenchymal stemcells ( MSCs) in rats with bleomycin-induced pulmonary fibrosis. Methods Bone marrowmesenchymal stemcells ( BMSCs) were harvested from6-week old male SD rats and cultured in vitro for the experiment. 48 SD rats were randomly divided into 4 groups, ie.a negative control group ( N) , a positive control group/bleomycin group ( B) , a MSCs grafting group ( M) ,and an IGF-1 treated MSCs grafting group ( I) . The rats in group B, M and I were intratracheally injected with bleomycin ( 1 mL,5 mg/kg) to induce pulmonary fibrosis. Group N were given saline as control. Group M/ I were injected the suspension of the CM-Dil labled-MSCs ( with no treatment/pre-incubated with IGF-1 for 48 hours) ( 0. 5mL,2 ×106 ) via the tail vein 2 days after injected bleomycin, and group B were injected with saline ( 0. 5 mL) simultaneously. The rats were sacrificed at 7,14,28 days after modeling. The histological changes of lung tissue were studied by HE and Masson’s trichrome staining. Hydroxyproline level in lung tissue was measured by digestion method. Frozen sections were made to observe the distribution of BMSCs in lung tissue, and the mRNA expression of hepatocyte growth factor ( HGF) was assayed by RTPCR.Results It was found that the red fluorescence of BMSCs existed in group M and I under the microscope and the integrated of optical density ( IOD) of group I was higher than that of group M at any time point. But the fluorescence was attenuated both in group M and group I until day 28. In the earlier period, the alveolitis in group B was more severe than that in the two cells-grafting groups in which group I was obviously milder. But there was no significant difference among group I, M and group N on day 28.Pulmonary fibrosis in group B, Mand I was significantly more severe than that in group N on day 14, but itwas milder in group M and I than that in group B on day 28. Otherwise, no difference existed between the two cells-grafting groups all the time. The content of hydroxyproline in group B was significantly higher than that in the other three groups all through the experiment, while there was on significant difference betweengroup I and group N fromthe beginning to the end. The value of group M was higher than those of group I and group N in the earlier period but decreased to the level of negative control group on day 28. Content of HGF mRNA in group Nand group I was maintained at a low level during the whole experiment process. The expression of HGF mRNA in group I was comparable to group M on day 7 and exceeded on day 14, the difference of which was more remarkable on day 28. Conclusions IGF-1 can enhance the migratory capacity of MSCs which may be a more effective treatment of lung disease. The mechanismmight be relatedto the increasing expression of HGF in MSCs.
Objective To investigate the relationship between adipocyte fatty acid binding protein ( A-FABP) and obstructive sleep apnea hypopnea syndrome ( OSAHS) . Methods A total of 120 patients were recruited and underwent polysomnography. The groups were allocated according severity of OSAHS and obesity. Plasma A-FABP ( ng/mL) levels were measured by ELISA. The associations between A-FABP and AHI, BMI, LSaO2 , MSaO2 , neck collar, waist /hip ratio, insulin resistance index were analyzed. Results Plasma A-FAPB levels were significantly higher in the OSAHS group than in the non-OSAHS group of same weight, independent of age and gender. In the non-OSAHS group and the severe OSAHS group, plasma A-FABP levels of obesity persons were significantly higher than those without obesity, independent of age and gender. Plasma A-FAPB level was positively correlated with AHI, BMI, insulin resistance index, neck collar, SLT90% , and waist/hip ratio, but negatevely correlated with LSaO2 and MSaO2 in the OSAHS group. In the non-OSAHS group, plasma A-FAPB level was positively correlated with BMI and insulin resistance index. Conclusions Plasma A-FABP level is higher in patients with severe OSAHS. Plasma A-FABP level is positively correlated with BMI and insulin resistance index both in OSAHS and non-OSAHS patients.