To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric la...To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin （30 mg/kg）. After 8 weeks intervention with perindopril （AE, n=10） or valsartan （AR, n=10）, the islet function of the animals was evaluated by intravenous insulin release test （IVIRT）. The pancreases were immunohistochemically stained to analyze the content of insulin and vascular endothelial growth factor （VEGF） in the islets. The microvessel density （MVD） of islets was detected by counting CD34 positive cells. The hypoxia inducible factor （HIF）-1α mRNA expression in the islets was detected by RT-PCR. Compared with normal control group （NC, n=10）, the area under the curve for insulin from 0 to 30 min （AUCI0-30） of diabetes group （DM, n=8） was decreased by 66.3%; the insulin relative concentration （IRC） of βcell was decreased significantly; the relative content of VEGF was increased obviously [（–4.21±0.13） vs （–4.06±0.29）]; MVD in islets was decreased by 71.4%; the relative expression of HIF-1α mRNA was increased by 1.19 times （all P〈0.01）. Compared with DM group, the AUCI0-30 of AE and AR group was increased by 44.6% and 34.9% respectively; IRC was also increased significantly; the relative content of VEGF was decreased by 21.2% and 21.7% respectively; MVD was increased by 62.5% and 75.0% respectively; the relative expression of HIF-1α was decreased by 27.2% and 29.0% respectively （all P〈0.01 or P〈0.05）. There were no significant differences in the said indexes between group AE and AR. It is concluded that the blockade of RAS may ameliorate islets function of diabetic rats by increasing the MVD in islets.展开更多
Objective:To investigate the impact of combining liraglutide with metformin on the enhancement of pancreatic islet function in patients with type 2 diabetes and coronary heart disease.Methods:60 patients with type 2 d...Objective:To investigate the impact of combining liraglutide with metformin on the enhancement of pancreatic islet function in patients with type 2 diabetes and coronary heart disease.Methods:60 patients with type 2 diabetes and coronary heart disease admitted from February 2022 to August 2023 were selected as research subjects.They were randomly assigned to either control or treatment groups,with 30 patients in each.The control group received metformin alone,while the treatment group received liraglutide in combination with metformin.Various indicators,including blood sugar levels,pancreatic islet function,and cardiac function between the two groups were compared.Results:The results of FPG,2hPG,HbA1c,HOMA-IR,NT-proBNP,and LVEDD in the treatment group were lower than those in the control group,whereas the values of FINS,HOMA-β,E/A,and LVEF in the treatment group were higher than those in the control group(P<0.05).Conclusion:The use of liraglutide in combination with metformin significantly benefits patients with type 2 diabetes and coronary heart disease.It leads to improved pancreatic islet function,better blood sugar control,and enhanced cardiac function.This combination therapy is recommended for clinical adoption.展开更多
Imaging changes in the pancreas can provide valuable information about the status of islet beta-cell function in different pancreatic diseases,such as diabetes,pancreatitis,pancreatic cancer,fatty pancreas,and insulin...Imaging changes in the pancreas can provide valuable information about the status of islet beta-cell function in different pancreatic diseases,such as diabetes,pancreatitis,pancreatic cancer,fatty pancreas,and insulinoma.While imaging cannot directly measure beta-cell function;it can be used as a marker of disease progression and a tool to guide therapeutic interventions.As imaging techno-logies continue to advance,they will likely play an increasingly important role in diagnosing,monitoring,and managing diabetes.展开更多
AIM. To investigate the influence of heme oxygenase-1 （HO-1） gene transfer on the viability and function of cultured rat islets in vitro. METHODS： Islets were isolated from the pancreata of Sprague-Dawley rats by i...AIM. To investigate the influence of heme oxygenase-1 （HO-1） gene transfer on the viability and function of cultured rat islets in vitro. METHODS： Islets were isolated from the pancreata of Sprague-Dawley rats by intraductal collagenase digestion, and purified by discontinuous Ficoll density gradient centrifugation. Purified rat islets were transfected with adenoviral vectors containing human HO-1 gene （Ad- HO-1） or enhanced green fluorescent protein gene （Ad- EGFP）, and then cultured for seven days. Transfection was confirmed by fluorescence microscopy and Western blot. Islet viability was evaluated by acridine orange/ propidium iodide fluorescent staining. Glucose-stimulated insulin release was detected using insulin radioimmunoassay kits and was used to assess the function of islets. Stimulation index （SI） was calculated by dividing the insulin release upon high glucose stimulation by the insulin release upon low glucose stimulation. RESULTS： After seven days culture, the viability of cultured rat islets decreased significantly （92% ± 6% vs 52% ± 13%, P 〈 0.05）, and glucose-stimulated insulin release also decreased significantly （6.47 ± 0.55 mIU/ L/30IEO vs 4.57 ± 0.40 mIU/L/3OIEO., 14.93 ± 1.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. Transfection of rat islets with adenoviral vectors at an 1±10 of 20 was efficient, and did not impair islet function. At 7 d post-transfection, the viability of Ad-HO-1 transfected islets was higher than that of control islets（71% ± 15% vs 52% ± 13%, P 〈 0.05）. There was no significant difference in insulin release upon low glucose stimulation （2.8 mmol/L） among Ad-HO-1 transfected group, Ad-EGFP transfected group, and control group （P 〉 0.05）, while when stimulated by high glucose （16.7 mmol/L） solution, insulin release in Ad-HO-1 transfected group was significantly higher than that in Ad-EGFP transfected group and control group, respectively （12.50 ±2.17 mIU/L/30IEQ vs 8.87 ± 0.65 mIU/L/30IEQ, 12.50 ± 2.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. The SI of Ad-HO-1 transfected group was also significantly higher than that of Ad-EGFP transfected group and control group, respectively （2.21 ± 0.02 vs 2.08 ± 0.05; 2.21 ± 0.02 vs 2.11 ± 0.03, P 〈 0.05）. CONCLUSION： The viability and function of rat islets decrease over time in in vitro culture, and heine oxygenase-1 gene transfer could improve the viability and function of cultured rat islets.展开更多
AIM： To evaluate the recovery and function of isolated rat pancreatic islets during in vitro culture with small intestinal submucosa （SIS）. METHODS： Pancreatic islets were isolated from Wistar rats by standard sur...AIM： To evaluate the recovery and function of isolated rat pancreatic islets during in vitro culture with small intestinal submucosa （SIS）. METHODS： Pancreatic islets were isolated from Wistar rats by standard surgical procurement followed by intraductal collagenase distension, mechanical dissociation and Euroficoll purification. Purified islets were cultured in plates coated with multilayer SIS （SIS-treated group） or without multilayer SIS （standard cultured group） for 7 and 14 d in standard islet culture media of RPMI 1640. After isolation and culture, islets from both experimental groups were stained with dithizone and counted. Recovery of islets was determined by the ratio of counts after the culture to the yield of islets immediately following islet isolation. Viability of islets after the culture was assessed by the glucose challenge best with low （2.7 mmol/L） and high glucose （16.7 mmol/L） solution supplemented with 50 mmol/L 3-isobutyl-1- methylxanthine （IBMX） solution. Apoptosis of islet cells after the culture was measured by relative quantification of histone-complexed DNA fragments using ELISA. RESULTS： After 7 or 14 d of in vitro tissue culture, the recovery of islets in SIS-treated group was significantly higher than that cultured in plates without SIS coating. The recovery of islets in SIS-treated group was about twice more than that of in the control group. In SIS treated group, there was no significant difference in the recovery of islets between short- and long-term periods of culture （95.8±1.0% vs 90.8±1.5%, P〉0.05）. When incubated with high glucose （16.7 mmol/L） solution, insulin secretion in SIS-treated group showed a higher increase than that in control group after 14 d of culture （20.7±1.1 mU/L vs 11.8±1.1 mU/L, P〈0.05）. When islets were placed in high glucose solution containing IBMX, stimulated insulin secretion was higher in SlS-treated group than in control group. Calculated stimulation index of SlS-treated group was about 23 times of control group. In addition, the stimulation index of SlS-treated group remained constant regardless of short- and long- term periods of culture （9.5±0.2 vs 10.2±1.2, P〉0.05）. Much less apoptosis of islet cells occurred in SlS-treated group than in control group after the culture. CONCLUSION： Co-culture of isolated rat islets with native sheet-like SIS might build an extracellular matrix for islets and provide possible biotrophic and growth factors that promote the recovery and subsequent function of islets.展开更多
Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with typ...Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with type 2 diabetes （T2D） were recruited in this study. T2D patients were divided into two groups according to therapy： 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intra- venous injection of 1 mg of ghicagon. Results Both fasting and 6-minute post-ghicagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients （0. 76±0. 36 ng/mL vs. 1.81±0. 78 ng/mL, P 〈 0.05 ; 0.88±0.42 ng/mL vs. 3.68±0. 98 ng/mL, P 〈 0. 05 ）. In T1D patients, the C-peptide level after injection of ghicagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy （2.45±0. 93 ng/mL vs. 1.61±0. 68 ng/mL, P 〈 0.05 ; 5.26±1.24 ng/mL vs. 2.15±0.76 ng/mL, P 〈 0.05 ）. The serum C-peptide level after ghicagon stimulation was positively correlated with C-peptide levels at fasting in all three groups （ r = 0.76, P 〈 0.05 ）. Conclusions The 6-minute ghicagon test is valuable in assessing the function of islet β cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.展开更多
Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and n...Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.展开更多
OBJECTIVE: To review the current progress of islet cell transplantation in patients with insulin-dependent diabetes, emphasizing on the difficulties with recovering and preserving islet cell mass and function, 30% of ...OBJECTIVE: To review the current progress of islet cell transplantation in patients with insulin-dependent diabetes, emphasizing on the difficulties with recovering and preserving islet cell mass and function, 30% of which is lost during the peri-transplantation period. RESULTS: The islet-cell isolation technique is perfected, but improvements are still progressing in two major directions: preservation of islet cells and tolerance induction. Optimum islet cell viability and function depends on appropriate revascularization of the islet graft and blockade of thrombus formation as well as cytokine and free radical release. Conditioning the islet cells in-vitro prior to transplantation to either upregulate VEGF expression or downregulate NF-kappa B transcription factor has proven to improve revascularization and to prevent islet cell apoptosis and cytokine-mediated damage. Tolerance induction is currently being best achieved by selecting and combining immunosuppressive agents such as monoclonal antibodies which target the major signaling molecules during immune activation, but which are least toxic to islet cells. CONCLUSIONS: Patients with insulin-dependent diabetes will greatly benefit from current developments in effective approaches to protect islets during the peritransplant period. Emerging interest in stem cell biology and differentiation may provide the ultimate solution to the problem of organ scarcity and islet cell protection from the peritransplant induced damage.展开更多
BACKGROUND At present,the existing internal medicine drug treatment can alleviate the high glucose toxicity of patients to a certain extent,to explore the efficacy of laparoscopic jejunoileal side to side anastomosis ...BACKGROUND At present,the existing internal medicine drug treatment can alleviate the high glucose toxicity of patients to a certain extent,to explore the efficacy of laparoscopic jejunoileal side to side anastomosis in the treatment of type 2 diabetes,the report is as follows.AIM To investigate the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes mellitus(T2DM).METHODS We retrospectively analyzed the clinical data of 78 patients with T2DM who were treated via jejunoileal lateral anastomosis.Metabolic indicators were collected preoperatively,as well as at 3 and 6 months postoperative.The metabolic indicators analyzed included body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting blood glucose(FBG),2-hour blood glucose(PBG),glycated hemoglobin(HbA1c),fasting C-peptide,2-hour C-peptide(PCP),fasting insulin(Fins),2-hour insulin(Pins),insulin resistance index(HOMA-IR),βCellular function index(HOMA-β),alanine aminotransferase,aspartate aminotransferase,serum total cholesterol(TC),low-density lipoprotein cholesterol(L DL-C),triglycerides(TG),high-density lipoprotein,and uric acid(UA)levels.RESULTS SBP,DBP,PBG,HbA1c,LDL-C,and TG were all significantly lower 3 months postoperative vs preoperative values;body weight,BMI,SBP,DBP,FBG,PBG,HbA1c,TC,TG,UA,and HOMA-IR values were all significantly lower 6 months postoperative vs at 3 months;and PCP,Fins,Pins,and HOMA-βwere all significantly higher 6 months postoperative vs at 3 months(all P<0.05).CONCLUSION Side-to-side anastomosis of the jejunum and ileum can effectively treat T2DM and improve the metabolic index levels associated with it.展开更多
目的分析达格列净联合二甲双胍治疗初诊2型糖尿病(T2DM)的临床效果及对患者胰岛功能、血脂水平的影响。方法选择我院2021年12月至2022年12月收治的72例初诊T2DM患者作为研究对象,以随机数字表法将其分为对照组和研究组,各36例。对照组...目的分析达格列净联合二甲双胍治疗初诊2型糖尿病(T2DM)的临床效果及对患者胰岛功能、血脂水平的影响。方法选择我院2021年12月至2022年12月收治的72例初诊T2DM患者作为研究对象,以随机数字表法将其分为对照组和研究组,各36例。对照组接受盐酸二甲双胍缓释片治疗,研究组在对照组基础上采用达格列净片治疗。比较两组的治疗效果。结果治疗后,研究组的空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)水平及胰岛素抵抗指数(HOMA-IR)低于对照组,胰岛β细胞功能指数(HOMA-β)高于对照组(P<0.05)。治疗后,研究组的丙二醛(MDA)、晚期氧化蛋白产物(AOPP)水平、miR-29a、miR-503、miR-9-3p表达水平低于对照组,miR-126表达水平高于对照组(P<0.05)。两组的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论达格列净联合二甲双胍治疗初诊T2DM患者能改善血糖、血脂、胰岛功能异常情况,还能调控miRNA表达水平,临床疗效确切,应用价值较高。展开更多
In this article,we comment on an article by Wang et al published in the World Journal of Diabetes.Existing treatments with oral medications can partially mitigate the toxicity of elevated blood glucose levels in patie...In this article,we comment on an article by Wang et al published in the World Journal of Diabetes.Existing treatments with oral medications can partially mitigate the toxicity of elevated blood glucose levels in patients with type 2 diabetes mellitus.However,these patients often require lifelong,costly medications,and many struggle with poor compliance.To address the limitations of pharmacological treatments,laparoscopic jejunal-ileal lateral anastomosis has become increasingly common in clinical practice and generally yields favorable outcomes.This procedure stimulates the secretion of larger amounts of glucagon-like peptide-1 by intestinal L cells,which in turn promotes pancreatic islet cell proliferation,reduces insulin resistance,and effectively controls glucose and lipid metabolism disorders.Nonetheless,further research is needed to fully explore its indications,contraindications,the enhancement of patients'quality of life and patients’satisfaction with the subjective experience of treatment and long-term effects.展开更多
目的探讨利拉鲁肽注射剂联合阿卡波糖、二甲双胍治疗2型糖尿病的临床效果及对胰岛功能、外周血皮质醇、血管紧张素Ⅱ(AngⅡ)水平的影响。方法选取2021年1月至2023年12月收治的2型糖尿病患者80例,随机分为观察组和对照组,每组40例。对照...目的探讨利拉鲁肽注射剂联合阿卡波糖、二甲双胍治疗2型糖尿病的临床效果及对胰岛功能、外周血皮质醇、血管紧张素Ⅱ(AngⅡ)水平的影响。方法选取2021年1月至2023年12月收治的2型糖尿病患者80例,随机分为观察组和对照组,每组40例。对照组予阿卡波糖联合二甲双胍治疗,观察组在此基础上予利拉鲁肽注射剂治疗。比较2组临床疗效、安全性及治疗前、治疗3个月、6个月空腹血糖、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)、三酰甘油、极低密度脂蛋白胆固醇(VLDL-C)、总胆固醇、胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)、胰岛素敏感指数(ISI)、微炎症状态[NOD样受体家族蛋白3炎性小体(NLRP3)、白细胞介素(IL)-1β、IL-18]及外周血AngⅡ、皮质醇水平。结果观察组总有效率[95.00%(38/40)]高于对照组[77.50%(31/40)],差异有统计学意义(P<0.05);2组不良反应总发生率比较差异无统计学意义(P>0.05)。与治疗前比较,2组治疗3、6个月空腹血糖、2 h PG、HbA1c、三酰甘油、VLDL-C、总胆固醇均下降,且观察组下降幅度较对照组大(P<0.05)。与治疗前比较,2组治疗3、6个月HOMA-IR、AngⅡ、皮质醇明显下降,HOMA-β、ISI显著升高;且观察组HOMA-IR、AngⅡ、皮质醇下降幅度较对照组大,HOMA-β、ISI升高幅度均较对照组大(P<0.05)。与治疗前比较,2组治疗3、6个月血清NLRP3、IL-1β、IL-18均明显下降,且观察组下降幅度较对照组大(P<0.05)。结论利拉鲁肽注射剂联合阿卡波糖、二甲双胍治疗2型糖尿病可减轻机体炎症反应,调节外周血AngⅡ、皮质醇水平,改善糖脂代谢,促进胰岛功能恢复。展开更多
基金supported by a grant from the Provincial Natural Sciences Foundation of Hubei, China (No 2005ABA158)
文摘To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin （30 mg/kg）. After 8 weeks intervention with perindopril （AE, n=10） or valsartan （AR, n=10）, the islet function of the animals was evaluated by intravenous insulin release test （IVIRT）. The pancreases were immunohistochemically stained to analyze the content of insulin and vascular endothelial growth factor （VEGF） in the islets. The microvessel density （MVD） of islets was detected by counting CD34 positive cells. The hypoxia inducible factor （HIF）-1α mRNA expression in the islets was detected by RT-PCR. Compared with normal control group （NC, n=10）, the area under the curve for insulin from 0 to 30 min （AUCI0-30） of diabetes group （DM, n=8） was decreased by 66.3%; the insulin relative concentration （IRC） of βcell was decreased significantly; the relative content of VEGF was increased obviously [（–4.21±0.13） vs （–4.06±0.29）]; MVD in islets was decreased by 71.4%; the relative expression of HIF-1α mRNA was increased by 1.19 times （all P〈0.01）. Compared with DM group, the AUCI0-30 of AE and AR group was increased by 44.6% and 34.9% respectively; IRC was also increased significantly; the relative content of VEGF was decreased by 21.2% and 21.7% respectively; MVD was increased by 62.5% and 75.0% respectively; the relative expression of HIF-1α was decreased by 27.2% and 29.0% respectively （all P〈0.01 or P〈0.05）. There were no significant differences in the said indexes between group AE and AR. It is concluded that the blockade of RAS may ameliorate islets function of diabetic rats by increasing the MVD in islets.
文摘Objective:To investigate the impact of combining liraglutide with metformin on the enhancement of pancreatic islet function in patients with type 2 diabetes and coronary heart disease.Methods:60 patients with type 2 diabetes and coronary heart disease admitted from February 2022 to August 2023 were selected as research subjects.They were randomly assigned to either control or treatment groups,with 30 patients in each.The control group received metformin alone,while the treatment group received liraglutide in combination with metformin.Various indicators,including blood sugar levels,pancreatic islet function,and cardiac function between the two groups were compared.Results:The results of FPG,2hPG,HbA1c,HOMA-IR,NT-proBNP,and LVEDD in the treatment group were lower than those in the control group,whereas the values of FINS,HOMA-β,E/A,and LVEF in the treatment group were higher than those in the control group(P<0.05).Conclusion:The use of liraglutide in combination with metformin significantly benefits patients with type 2 diabetes and coronary heart disease.It leads to improved pancreatic islet function,better blood sugar control,and enhanced cardiac function.This combination therapy is recommended for clinical adoption.
文摘Imaging changes in the pancreas can provide valuable information about the status of islet beta-cell function in different pancreatic diseases,such as diabetes,pancreatitis,pancreatic cancer,fatty pancreas,and insulinoma.While imaging cannot directly measure beta-cell function;it can be used as a marker of disease progression and a tool to guide therapeutic interventions.As imaging techno-logies continue to advance,they will likely play an increasingly important role in diagnosing,monitoring,and managing diabetes.
基金Supported by the National Natural Science Foundation of China, No. 30571759Social Development Foundation of Shanghai, No. 200253
文摘AIM. To investigate the influence of heme oxygenase-1 （HO-1） gene transfer on the viability and function of cultured rat islets in vitro. METHODS： Islets were isolated from the pancreata of Sprague-Dawley rats by intraductal collagenase digestion, and purified by discontinuous Ficoll density gradient centrifugation. Purified rat islets were transfected with adenoviral vectors containing human HO-1 gene （Ad- HO-1） or enhanced green fluorescent protein gene （Ad- EGFP）, and then cultured for seven days. Transfection was confirmed by fluorescence microscopy and Western blot. Islet viability was evaluated by acridine orange/ propidium iodide fluorescent staining. Glucose-stimulated insulin release was detected using insulin radioimmunoassay kits and was used to assess the function of islets. Stimulation index （SI） was calculated by dividing the insulin release upon high glucose stimulation by the insulin release upon low glucose stimulation. RESULTS： After seven days culture, the viability of cultured rat islets decreased significantly （92% ± 6% vs 52% ± 13%, P 〈 0.05）, and glucose-stimulated insulin release also decreased significantly （6.47 ± 0.55 mIU/ L/30IEO vs 4.57 ± 0.40 mIU/L/3OIEO., 14.93 ± 1.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. Transfection of rat islets with adenoviral vectors at an 1±10 of 20 was efficient, and did not impair islet function. At 7 d post-transfection, the viability of Ad-HO-1 transfected islets was higher than that of control islets（71% ± 15% vs 52% ± 13%, P 〈 0.05）. There was no significant difference in insulin release upon low glucose stimulation （2.8 mmol/L） among Ad-HO-1 transfected group, Ad-EGFP transfected group, and control group （P 〉 0.05）, while when stimulated by high glucose （16.7 mmol/L） solution, insulin release in Ad-HO-1 transfected group was significantly higher than that in Ad-EGFP transfected group and control group, respectively （12.50 ±2.17 mIU/L/30IEQ vs 8.87 ± 0.65 mIU/L/30IEQ, 12.50 ± 2.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. The SI of Ad-HO-1 transfected group was also significantly higher than that of Ad-EGFP transfected group and control group, respectively （2.21 ± 0.02 vs 2.08 ± 0.05; 2.21 ± 0.02 vs 2.11 ± 0.03, P 〈 0.05）. CONCLUSION： The viability and function of rat islets decrease over time in in vitro culture, and heine oxygenase-1 gene transfer could improve the viability and function of cultured rat islets.
基金Supported by the Key Program of Science and Technique of Ministry of Education of the People's Republic of China, No.104169
文摘AIM： To evaluate the recovery and function of isolated rat pancreatic islets during in vitro culture with small intestinal submucosa （SIS）. METHODS： Pancreatic islets were isolated from Wistar rats by standard surgical procurement followed by intraductal collagenase distension, mechanical dissociation and Euroficoll purification. Purified islets were cultured in plates coated with multilayer SIS （SIS-treated group） or without multilayer SIS （standard cultured group） for 7 and 14 d in standard islet culture media of RPMI 1640. After isolation and culture, islets from both experimental groups were stained with dithizone and counted. Recovery of islets was determined by the ratio of counts after the culture to the yield of islets immediately following islet isolation. Viability of islets after the culture was assessed by the glucose challenge best with low （2.7 mmol/L） and high glucose （16.7 mmol/L） solution supplemented with 50 mmol/L 3-isobutyl-1- methylxanthine （IBMX） solution. Apoptosis of islet cells after the culture was measured by relative quantification of histone-complexed DNA fragments using ELISA. RESULTS： After 7 or 14 d of in vitro tissue culture, the recovery of islets in SIS-treated group was significantly higher than that cultured in plates without SIS coating. The recovery of islets in SIS-treated group was about twice more than that of in the control group. In SIS treated group, there was no significant difference in the recovery of islets between short- and long-term periods of culture （95.8±1.0% vs 90.8±1.5%, P〉0.05）. When incubated with high glucose （16.7 mmol/L） solution, insulin secretion in SIS-treated group showed a higher increase than that in control group after 14 d of culture （20.7±1.1 mU/L vs 11.8±1.1 mU/L, P〈0.05）. When islets were placed in high glucose solution containing IBMX, stimulated insulin secretion was higher in SlS-treated group than in control group. Calculated stimulation index of SlS-treated group was about 23 times of control group. In addition, the stimulation index of SlS-treated group remained constant regardless of short- and long- term periods of culture （9.5±0.2 vs 10.2±1.2, P〉0.05）. Much less apoptosis of islet cells occurred in SlS-treated group than in control group after the culture. CONCLUSION： Co-culture of isolated rat islets with native sheet-like SIS might build an extracellular matrix for islets and provide possible biotrophic and growth factors that promote the recovery and subsequent function of islets.
文摘Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with type 2 diabetes （T2D） were recruited in this study. T2D patients were divided into two groups according to therapy： 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intra- venous injection of 1 mg of ghicagon. Results Both fasting and 6-minute post-ghicagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients （0. 76±0. 36 ng/mL vs. 1.81±0. 78 ng/mL, P 〈 0.05 ; 0.88±0.42 ng/mL vs. 3.68±0. 98 ng/mL, P 〈 0. 05 ）. In T1D patients, the C-peptide level after injection of ghicagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy （2.45±0. 93 ng/mL vs. 1.61±0. 68 ng/mL, P 〈 0.05 ; 5.26±1.24 ng/mL vs. 2.15±0.76 ng/mL, P 〈 0.05 ）. The serum C-peptide level after ghicagon stimulation was positively correlated with C-peptide levels at fasting in all three groups （ r = 0.76, P 〈 0.05 ）. Conclusions The 6-minute ghicagon test is valuable in assessing the function of islet β cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.
基金grants from the National Natural Science Foundation of China(No.81270885,No.81570726 and No.81600609)Shanghai Jiao Tong University School of Medicine(2014)+4 种基金the Ministry of Science and Technology in China(No.2012CB524906)the Science and Technology Commission of Shanghai Municipality(No.14495810700 and No.16410723200)Three-year Action Plan for Public Health System Construction in Shanghai by Shanghai Municipal Commission of Health and Family Planning(2015-2017)Clinical Potential Subject Construction of Shanghai Jiao Tong University School of Medicine(2014),Shanghai Municipal Health Bureau of China(No.20124262)Seed Founding of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine(No.JYZZ032).
文摘Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.
文摘OBJECTIVE: To review the current progress of islet cell transplantation in patients with insulin-dependent diabetes, emphasizing on the difficulties with recovering and preserving islet cell mass and function, 30% of which is lost during the peri-transplantation period. RESULTS: The islet-cell isolation technique is perfected, but improvements are still progressing in two major directions: preservation of islet cells and tolerance induction. Optimum islet cell viability and function depends on appropriate revascularization of the islet graft and blockade of thrombus formation as well as cytokine and free radical release. Conditioning the islet cells in-vitro prior to transplantation to either upregulate VEGF expression or downregulate NF-kappa B transcription factor has proven to improve revascularization and to prevent islet cell apoptosis and cytokine-mediated damage. Tolerance induction is currently being best achieved by selecting and combining immunosuppressive agents such as monoclonal antibodies which target the major signaling molecules during immune activation, but which are least toxic to islet cells. CONCLUSIONS: Patients with insulin-dependent diabetes will greatly benefit from current developments in effective approaches to protect islets during the peritransplant period. Emerging interest in stem cell biology and differentiation may provide the ultimate solution to the problem of organ scarcity and islet cell protection from the peritransplant induced damage.
文摘BACKGROUND At present,the existing internal medicine drug treatment can alleviate the high glucose toxicity of patients to a certain extent,to explore the efficacy of laparoscopic jejunoileal side to side anastomosis in the treatment of type 2 diabetes,the report is as follows.AIM To investigate the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes mellitus(T2DM).METHODS We retrospectively analyzed the clinical data of 78 patients with T2DM who were treated via jejunoileal lateral anastomosis.Metabolic indicators were collected preoperatively,as well as at 3 and 6 months postoperative.The metabolic indicators analyzed included body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting blood glucose(FBG),2-hour blood glucose(PBG),glycated hemoglobin(HbA1c),fasting C-peptide,2-hour C-peptide(PCP),fasting insulin(Fins),2-hour insulin(Pins),insulin resistance index(HOMA-IR),βCellular function index(HOMA-β),alanine aminotransferase,aspartate aminotransferase,serum total cholesterol(TC),low-density lipoprotein cholesterol(L DL-C),triglycerides(TG),high-density lipoprotein,and uric acid(UA)levels.RESULTS SBP,DBP,PBG,HbA1c,LDL-C,and TG were all significantly lower 3 months postoperative vs preoperative values;body weight,BMI,SBP,DBP,FBG,PBG,HbA1c,TC,TG,UA,and HOMA-IR values were all significantly lower 6 months postoperative vs at 3 months;and PCP,Fins,Pins,and HOMA-βwere all significantly higher 6 months postoperative vs at 3 months(all P<0.05).CONCLUSION Side-to-side anastomosis of the jejunum and ileum can effectively treat T2DM and improve the metabolic index levels associated with it.
文摘目的分析达格列净联合二甲双胍治疗初诊2型糖尿病(T2DM)的临床效果及对患者胰岛功能、血脂水平的影响。方法选择我院2021年12月至2022年12月收治的72例初诊T2DM患者作为研究对象,以随机数字表法将其分为对照组和研究组,各36例。对照组接受盐酸二甲双胍缓释片治疗,研究组在对照组基础上采用达格列净片治疗。比较两组的治疗效果。结果治疗后,研究组的空腹血糖(FBG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)、总胆固醇(TC)、甘油三酯(TG)水平及胰岛素抵抗指数(HOMA-IR)低于对照组,胰岛β细胞功能指数(HOMA-β)高于对照组(P<0.05)。治疗后,研究组的丙二醛(MDA)、晚期氧化蛋白产物(AOPP)水平、miR-29a、miR-503、miR-9-3p表达水平低于对照组,miR-126表达水平高于对照组(P<0.05)。两组的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论达格列净联合二甲双胍治疗初诊T2DM患者能改善血糖、血脂、胰岛功能异常情况,还能调控miRNA表达水平,临床疗效确切,应用价值较高。
文摘In this article,we comment on an article by Wang et al published in the World Journal of Diabetes.Existing treatments with oral medications can partially mitigate the toxicity of elevated blood glucose levels in patients with type 2 diabetes mellitus.However,these patients often require lifelong,costly medications,and many struggle with poor compliance.To address the limitations of pharmacological treatments,laparoscopic jejunal-ileal lateral anastomosis has become increasingly common in clinical practice and generally yields favorable outcomes.This procedure stimulates the secretion of larger amounts of glucagon-like peptide-1 by intestinal L cells,which in turn promotes pancreatic islet cell proliferation,reduces insulin resistance,and effectively controls glucose and lipid metabolism disorders.Nonetheless,further research is needed to fully explore its indications,contraindications,the enhancement of patients'quality of life and patients’satisfaction with the subjective experience of treatment and long-term effects.
文摘目的探讨利拉鲁肽注射剂联合阿卡波糖、二甲双胍治疗2型糖尿病的临床效果及对胰岛功能、外周血皮质醇、血管紧张素Ⅱ(AngⅡ)水平的影响。方法选取2021年1月至2023年12月收治的2型糖尿病患者80例,随机分为观察组和对照组,每组40例。对照组予阿卡波糖联合二甲双胍治疗,观察组在此基础上予利拉鲁肽注射剂治疗。比较2组临床疗效、安全性及治疗前、治疗3个月、6个月空腹血糖、餐后2 h血糖(2 h PG)、糖化血红蛋白(HbA1c)、三酰甘油、极低密度脂蛋白胆固醇(VLDL-C)、总胆固醇、胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)、胰岛素敏感指数(ISI)、微炎症状态[NOD样受体家族蛋白3炎性小体(NLRP3)、白细胞介素(IL)-1β、IL-18]及外周血AngⅡ、皮质醇水平。结果观察组总有效率[95.00%(38/40)]高于对照组[77.50%(31/40)],差异有统计学意义(P<0.05);2组不良反应总发生率比较差异无统计学意义(P>0.05)。与治疗前比较,2组治疗3、6个月空腹血糖、2 h PG、HbA1c、三酰甘油、VLDL-C、总胆固醇均下降,且观察组下降幅度较对照组大(P<0.05)。与治疗前比较,2组治疗3、6个月HOMA-IR、AngⅡ、皮质醇明显下降,HOMA-β、ISI显著升高;且观察组HOMA-IR、AngⅡ、皮质醇下降幅度较对照组大,HOMA-β、ISI升高幅度均较对照组大(P<0.05)。与治疗前比较,2组治疗3、6个月血清NLRP3、IL-1β、IL-18均明显下降,且观察组下降幅度较对照组大(P<0.05)。结论利拉鲁肽注射剂联合阿卡波糖、二甲双胍治疗2型糖尿病可减轻机体炎症反应,调节外周血AngⅡ、皮质醇水平,改善糖脂代谢,促进胰岛功能恢复。
