Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan...Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.展开更多
BACKGROUND Despite the increased use of total pancreatectomy with islet autotransplantation(TPIAT),systematic evidence of its outcomes remains limited.AIM To evaluate the outcomes of TPIAT.METHODS We searched PubMed,E...BACKGROUND Despite the increased use of total pancreatectomy with islet autotransplantation(TPIAT),systematic evidence of its outcomes remains limited.AIM To evaluate the outcomes of TPIAT.METHODS We searched PubMed,EMBASE,and Cochrane databases from inception through March 2019 for studies on TPIAT outcomes.Data were extracted and analyzed using comprehensive meta-analysis software.The random-effects model was used for all variables.Heterogeneity was assessed using the I2 measure and Cochrane Q-statistic.Publication bias was assessed using Egger’s test.RESULTS Twenty-one studies published between 1980 and 2017 examining 1011 patients were included.Eighteen studies were of adults,while three studied pediatric populations.Narcotic independence was achieved in 53.5%[95% Confidence Interval(CI):45-62,P<0.05,I2=81%]of adults compared to 51.9%(95%CI:17-85,P<0.05,I2=84%)of children.Insulinindependence post-procedure was achieved in 31.8%(95%CI:26-38,P<0.05,I2=64%)of adults with considerable heterogeneity compared to 47.7%(95%CI:20-77,P<0.05,I2=82%)in children.Glycated hemoglobin(HbA1C)12 mo post-surgery was reported in four studies with a pooled value of 6.76%(P=0.27).Neither stratification by age of the studied population nor metaregression analysis considering both the study publication date and the islet-cell-equivalent/kg weight explained the marked heterogeneity between studies.CONCLUSION These results indicate acceptable success for TPIAT.Future studies should evaluate the discussed measures before and after surgery for comparison.展开更多
Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes(T1D)by transplanting pancreatic beta cells.Overall,pancreatic isl...Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes(T1D)by transplanting pancreatic beta cells.Overall,pancreatic islet transplantation has improved to a great extent,and cellular replacement will likely become the mainstay treatment.We review pancreatic islet transplantation as a treatment for T1D and the immunological challenges faced.Published data demonstrated that the time for islet cell transfusion varied between 2 and 10 h.Approximately 54%of the patients gained insulin independence at the end of the first year,while only 20%remained insulin-free at the end of the second year.Eventually,most transplanted patients return to using some form of exogenous insulin within a few years after the transplantation,which imposed the need to improve immunological factors before transplantation.We also discuss the immunosuppressive regimens,apoptotic donor lymphocytes,anti-TIM-1 antibodies,mixed chimerism-based tolerance induction,induction of antigen-specific tolerance utilizing ethylene carbodiimide-fixed splenocytes,pretransplant infusions of donor apoptotic cells,B cell depletion,preconditioning of isolated islets,inducing local immunotolerance,cell encapsulation and immunoisolation,using of biomaterials,immunomodulatory cells,etc.展开更多
Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T...Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T2D)patients.Methods A total of 4670 T2D patients from seven communities in Shanghai,China were enrolled.The anthropometric indices,biochemical parameters,serum 25(OH)D,and islet function[including C-peptide(C-p)and glucagon]were measured.Results The fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),glucagon,and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased.Next,the population was divided into two groups:abdominal obesity and non-abdominal obesity groups.After adjustment,the 25(OH)D level was found to be associated with HbA1c,glucagon,and homeostasis model assessment ofβ(HOMA-β)in the non-abdominal obesity group.There was a significant relationship between 25(OH)D and HbA1c,glucagon,HOMA-IR,baseline insulin or C-p in the abdominal obesity group.In the abdominal obesity group,the ordinary least squares(OLS)regression and quantile regression revealed that 25(OH)D was obviously associated with glucagon and fasting C-p levels.In the abdominal obesity group,the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p(P=0.0124).Furthermore,the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation(SD)below the mean(P=0.0002),and lower at the mean of the course of diabetes(P=0.0007).Conclusion 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity.The 25(OH)D influenced C-p in part by influencing glucagon.The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity,in terms of islet homeostasis,is influenced by the course of diabetes.展开更多
Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia.While multiple factors contribute to this predisposition,one of these involves the increased secretion of amylin,or islet amyloid po...Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia.While multiple factors contribute to this predisposition,one of these involves the increased secretion of amylin,or islet amyloid polypeptide,that accompanies the pathophysiology of type 2 diabetes mellitus.Islet amyloid polypeptide accumulation has undoubtedly been implicated in various forms of dementia,including Alzheimer’s disease and vascular dementia,but the exact mechanisms underlying islet amyloid polypeptide’s causative role in dementia are unclear.In this review,we have summarized the literature supporting the various mechanisms by which islet amyloid polypeptide accumulation may cause neuronal damage,ultimately leading to the clinical symptoms of dementia.We discuss the evidence for islet amyloid polypeptide deposition in the brain,islet amyloid polypeptide interaction with other amyloids implicated in neurodegeneration,neuroinflammation caused by islet amyloid polypeptide deposition,vascular damage induced by islet amyloid polypeptide accumulation,and islet amyloid polypeptide-induced cytotoxicity.There are very few therapies approved for the treatment of dementia,and of these,clinical responses have been controversial at best.Therefore,investigating new,targetable pathways is vital for identifying novel therapeutic strategies for treating dementia.As such,we conclude this review by discussing islet amyloid polypeptide accumulation as a potential therapeutic target not only in treating type 2 diabetes mellitus but as a future target in treating or even preventing dementia associated with type 2 diabetes mellitus.展开更多
To the Editor:Total pancreatectomy with islet cell autotransplantation(TPIAT)is a viable treatment option upon failed endoscopic and medical therapy for patients with chronic pancreatitis.This procedure involves surgi...To the Editor:Total pancreatectomy with islet cell autotransplantation(TPIAT)is a viable treatment option upon failed endoscopic and medical therapy for patients with chronic pancreatitis.This procedure involves surgical removal of the entire pancreas,isolation of islet cells and reinfusion of these cells into the liver via portal vein[1,2].The risk of contamination to the final islet cell product can occur at several stages of the isolation procedure[3].In order to ensure the sterility of the islet cell product,multiple samples from the preservation and cannulation solution,and the final islet cell product are sent for bacterial cultures.Prior studies have found variable clinical consequences of these cultures on infectious com-plications or graft function[3-9].Herein we aimed to determine the incidence of infection in 60 days post-TPIAT and its association with the culture data.展开更多
Diabetes mellitus is a global health problem resulting from islet dysfunction or insulin resistance.The mechanisms of islet dysfunction are still under investigation.Islet hormone secretion is the main function of isl...Diabetes mellitus is a global health problem resulting from islet dysfunction or insulin resistance.The mechanisms of islet dysfunction are still under investigation.Islet hormone secretion is the main function of islets,and serves an important role in the homeostasis of blood glucose.Elucidating the detailed mechanism of islet hormone secretome distortion can provide clues for the treatment of diabetes.Therefore,it is crucial to develop accurate,real-time,laborsaving,high-throughput,automated,and cost-effective techniques for the sensing of islet secretome.Microfluidic chips,an elegant platform that combines biology,engineering,computer science,and biomaterials,have attracted tremendous interest from scientists in the field of diabetes worldwide.These tiny devices are miniatures of traditional experimental systems with more advantages of timesaving,reagent-minimization,automation,high-throughput,and online detection.These features of microfluidic chips meet the demands of islet secretome analysis and a variety of chips have been designed in the past 20 years.In this review,we present a brief introduction of microfluidic chips,and three microfluidic chipsbased islet hormone sensing techniques.We focus mainly on the theory of these techniques,and provide detailed examples based on these theories with the hope of providing some insights into the design of future chips or whole detection systems.展开更多
BACKGROUND Islet amyloid deposition and reducedβ-cell mass are pathological hallmarks in type 2 diabetes mellitus subjects.To date,the pathological features of the islets in diabetes secondary to pancreatic ductal ad...BACKGROUND Islet amyloid deposition and reducedβ-cell mass are pathological hallmarks in type 2 diabetes mellitus subjects.To date,the pathological features of the islets in diabetes secondary to pancreatic ductal adenocarcinoma(PDAC)have not been specifically addressed.AIM To provide further insight into the relationship between islet amyloid deposition of the residual pancreas in PDAC patients and to explore whether regional differences(proximal vs distal residual pancreas)are associated with islet amyloid deposition.METHODS We retrospectively collected clinical information and pancreatic tissue removed from tumors of 45 PDAC patients,including 14 patients with normal glucose tolerance(NGT),16 patients with prediabetes and 15 new-onset diabetes(NOD)patients diagnosed before surgery by an oral glucose tolerance test at West China Hospital from July 2017 to June 2020.Pancreatic volume was calculated by multiplying the estimated area of pancreatic tissue on each image slice by the interval between slices based on abdominal computer tomography scans.Several sections of paraffin-embedded pancreas specimens from both the proximal and/or distal regions remote from the tumor were stained as follows:(1)Hematoxylin and eosin for general histological appearance;(2)hematoxylin and insulin for the determination of fractionalβ-cell area(immunohistochemistry);and(3)quadruple insulin,glucagon,thioflavin T and DAPI staining for the determination ofβ-cell area,α-cell area and amyloid deposits.RESULTS Screening for pancreatic histologic features revealed that duct obstruction with islet amyloid deposition,fibrosis and marked acinar atrophy were robust in the distal pancreatic regions but much less robust in the proximal regions,especially in the prediabetes and NOD groups.Consistent with this finding,the remnant pancreatic volume was markedly decreased in the NOD group by nearly one-half compared with that in the NGT group(37.35±12.16 cm^(3) vs 69.79±18.17 cm^(3),P<0.001).As expected,islets that stained positive for amyloid(islet amyloid density)were found in the majority of PDAC cases.The proportion of amyloid/islet area(severity of amyloid deposition)was significantly higher in both prediabetes and NOD patients than in NGT patients(P=0.002;P<0.0001,respectively).We further examined the regional differences in islet amyloid deposits.Islet amyloid deposit density was robustly increased by approximately 8-fold in the distal regions compared with that in the proximal regions in the prediabetes and NOD groups(3.98%±3.39%vs 0.50%±0.72%,P=0.01;12.03%vs 1.51%,P=0.001,respectively).CONCLUSION In conclusion,these findings suggest that robust alterations of the distal pancreas due to tumors can disturb islet function and structure with islet amyloid formation,which may be associated with the pathogenesis of NOD secondary to PDAC.展开更多
A century has passed since the Nobel Prize winning discovery of insulin,which still remains the mainstay treatment for type 1 diabetes mellitus(T1DM)to this day.True to the words of its discoverer Sir Frederick Banti...A century has passed since the Nobel Prize winning discovery of insulin,which still remains the mainstay treatment for type 1 diabetes mellitus(T1DM)to this day.True to the words of its discoverer Sir Frederick Banting,“insulin is not a cure for diabetes,it is a treatment”,millions of people with T1DM are dependent on daily insulin medications for life.Clinical donor islet transplantation has proven that T1DM is curable,however due to profound shortages of donor islets,it is not a mainstream treatment option for T1DM.Human pluripotent stem cell derived insulin-secreting cells,pervasively known as stem cell-derivedβcells(SC-βcells),are a promising alternative source and have the potential to become a T1DM treatment through cell replacement therapy.Here we briefly review how isletβcells develop and mature in vivo and several types of reported SC-βcells produced using different ex vivo protocols in the last decade.Although some markers of maturation were expressed and glucose stimulated insulin secretion was shown,the SC-βcells have not been directly compared to their in vivo counterparts,generally have limited glucose response,and are not yet fully matured.Due to the presence of extra-pancreatic insulin-expressing cells,and ethical and technological issues,further clarification of the true nature of these SC-βcells is required.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
目的探讨甘精胰岛素U300联合口服降糖药治疗2型糖尿病的临床效果。方法选择2021年10月—2023年1月广东省吴川市人民医院收治的79例2型糖尿病患者,随机分为非甘精组(39例)和U300组(40例)。非甘精组口服降糖药物治疗,在此之上,U300组增加...目的探讨甘精胰岛素U300联合口服降糖药治疗2型糖尿病的临床效果。方法选择2021年10月—2023年1月广东省吴川市人民医院收治的79例2型糖尿病患者,随机分为非甘精组(39例)和U300组(40例)。非甘精组口服降糖药物治疗,在此之上,U300组增加甘精胰岛素U300治疗,持续治疗3个月,对比2组血糖及相关指标变化,并监测患者胰岛素功能相关指标改善情况,评估低血糖反应等不良反应情况。结果治疗后,U300组血糖指标、血糖波动指标均显著低于非甘精组,差异有统计学意义(P<0.05)。U300组治疗后胰岛素功能指标均显著优于非甘精组,空腹及餐后2 h C肽均显著高于非甘精组,差异有统计学意义(P<0.05)。U300组低血糖反应发生率(2.50%,1/40)和不良反应总发生率(20.00%,8/40)与非甘精组(2.56,1/39;17.95%,7/39)比较,差异无统计学意义(P>0.05)。结论增加甘精胰岛素U300治疗,可更好地提升患者血糖管理效果,并可改善胰岛功能,有利于稳定控制血糖,有助于提高患者病情控制效果,应用效果安全可靠。展开更多
基金funded by the National Natural Science Foundation of China (32371341,31872674)the Scientific and Technologic Foundation of Jilin Province (20230202050NC)the Fundamental Research Funds for the Central Universities (CGZH202206)。
文摘Type 1 diabetes mellitus(T1DM) lacks insulin secretion due to autoimmune deficiency of pancreaticβ-cells.Protecting pancreatic islets and enhancing insulin secretion has been therapeutic approaches.Mannogalactoglucan is the main type of polysaccharide from natural mushroom,which has potential medicinal prospects.Nevertheless,the antidiabetic property of mannogalactoglucan in T1DM has not been fully elucidated.In this study,we obtained the neutral fraction of alkali-soluble Armillaria mellea polysaccharide(AAMP-N) with the structure of mannogalactoglucan from the fruiting body of A.mellea and investigated the potential therapeutic value of AAMP-N in T1DM.We demonstrated that AAMP-N lowered blood glucose and improved diabetes symptoms in T1DM mice.AAMP-N activated unfolded protein response(UPR) signaling pathway to maintain ER protein folding homeostasis and promote insulin secretion in vivo.Besides that,AAMP-N promoted insulin synthesis via upregulating the expression of transcription factors,increased Ca^(2+) signals to stimulate intracellular insulin secretory vesicle transport via activating calcium/calmodulin-dependent kinase Ⅱ(CamkⅡ) and cAMP/PKA signals,and enhanced insulin secretory vesicle fusion with the plasma membrane via vesicle-associated membrane protein 2(VAMP2).Collectively,these studies demonstrated that the therapeutic potential of AAMP-N on pancreatic islets function,indicating that mannogalactoglucan could be natural nutraceutical used for the treatment of T1DM.
文摘BACKGROUND Despite the increased use of total pancreatectomy with islet autotransplantation(TPIAT),systematic evidence of its outcomes remains limited.AIM To evaluate the outcomes of TPIAT.METHODS We searched PubMed,EMBASE,and Cochrane databases from inception through March 2019 for studies on TPIAT outcomes.Data were extracted and analyzed using comprehensive meta-analysis software.The random-effects model was used for all variables.Heterogeneity was assessed using the I2 measure and Cochrane Q-statistic.Publication bias was assessed using Egger’s test.RESULTS Twenty-one studies published between 1980 and 2017 examining 1011 patients were included.Eighteen studies were of adults,while three studied pediatric populations.Narcotic independence was achieved in 53.5%[95% Confidence Interval(CI):45-62,P<0.05,I2=81%]of adults compared to 51.9%(95%CI:17-85,P<0.05,I2=84%)of children.Insulinindependence post-procedure was achieved in 31.8%(95%CI:26-38,P<0.05,I2=64%)of adults with considerable heterogeneity compared to 47.7%(95%CI:20-77,P<0.05,I2=82%)in children.Glycated hemoglobin(HbA1C)12 mo post-surgery was reported in four studies with a pooled value of 6.76%(P=0.27).Neither stratification by age of the studied population nor metaregression analysis considering both the study publication date and the islet-cell-equivalent/kg weight explained the marked heterogeneity between studies.CONCLUSION These results indicate acceptable success for TPIAT.Future studies should evaluate the discussed measures before and after surgery for comparison.
基金Supported by European Union-NextGenerationEU,through The National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008-C01.
文摘Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes(T1D)by transplanting pancreatic beta cells.Overall,pancreatic islet transplantation has improved to a great extent,and cellular replacement will likely become the mainstay treatment.We review pancreatic islet transplantation as a treatment for T1D and the immunological challenges faced.Published data demonstrated that the time for islet cell transfusion varied between 2 and 10 h.Approximately 54%of the patients gained insulin independence at the end of the first year,while only 20%remained insulin-free at the end of the second year.Eventually,most transplanted patients return to using some form of exogenous insulin within a few years after the transplantation,which imposed the need to improve immunological factors before transplantation.We also discuss the immunosuppressive regimens,apoptotic donor lymphocytes,anti-TIM-1 antibodies,mixed chimerism-based tolerance induction,induction of antigen-specific tolerance utilizing ethylene carbodiimide-fixed splenocytes,pretransplant infusions of donor apoptotic cells,B cell depletion,preconditioning of isolated islets,inducing local immunotolerance,cell encapsulation and immunoisolation,using of biomaterials,immunomodulatory cells,etc.
基金supported by the National Natural Science Foundation of China(No.82120108008,No.91857117)the Project of Biobank(No.YBKA201909)from Shanghai Ninth People’s Hospital,Shanghai Jiaotong University School of Medicinea grant from Shanghai Jiaotong University School of Medicine(No.19XJ11007).
文摘Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T2D)patients.Methods A total of 4670 T2D patients from seven communities in Shanghai,China were enrolled.The anthropometric indices,biochemical parameters,serum 25(OH)D,and islet function[including C-peptide(C-p)and glucagon]were measured.Results The fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),glucagon,and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased.Next,the population was divided into two groups:abdominal obesity and non-abdominal obesity groups.After adjustment,the 25(OH)D level was found to be associated with HbA1c,glucagon,and homeostasis model assessment ofβ(HOMA-β)in the non-abdominal obesity group.There was a significant relationship between 25(OH)D and HbA1c,glucagon,HOMA-IR,baseline insulin or C-p in the abdominal obesity group.In the abdominal obesity group,the ordinary least squares(OLS)regression and quantile regression revealed that 25(OH)D was obviously associated with glucagon and fasting C-p levels.In the abdominal obesity group,the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p(P=0.0124).Furthermore,the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation(SD)below the mean(P=0.0002),and lower at the mean of the course of diabetes(P=0.0007).Conclusion 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity.The 25(OH)D influenced C-p in part by influencing glucagon.The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity,in terms of islet homeostasis,is influenced by the course of diabetes.
基金supported by The Mike Hogg FundBaylor College of Medicine Medical Scientist Training Program,NICHD R01HD099252(to RJP)and R01HD098131(to RJP)the NHLBI T32 HL092332(to ASB)。
文摘Type 2 diabetes mellitus patients have a markedly higher risk of developing dementia.While multiple factors contribute to this predisposition,one of these involves the increased secretion of amylin,or islet amyloid polypeptide,that accompanies the pathophysiology of type 2 diabetes mellitus.Islet amyloid polypeptide accumulation has undoubtedly been implicated in various forms of dementia,including Alzheimer’s disease and vascular dementia,but the exact mechanisms underlying islet amyloid polypeptide’s causative role in dementia are unclear.In this review,we have summarized the literature supporting the various mechanisms by which islet amyloid polypeptide accumulation may cause neuronal damage,ultimately leading to the clinical symptoms of dementia.We discuss the evidence for islet amyloid polypeptide deposition in the brain,islet amyloid polypeptide interaction with other amyloids implicated in neurodegeneration,neuroinflammation caused by islet amyloid polypeptide deposition,vascular damage induced by islet amyloid polypeptide accumulation,and islet amyloid polypeptide-induced cytotoxicity.There are very few therapies approved for the treatment of dementia,and of these,clinical responses have been controversial at best.Therefore,investigating new,targetable pathways is vital for identifying novel therapeutic strategies for treating dementia.As such,we conclude this review by discussing islet amyloid polypeptide accumulation as a potential therapeutic target not only in treating type 2 diabetes mellitus but as a future target in treating or even preventing dementia associated with type 2 diabetes mellitus.
文摘To the Editor:Total pancreatectomy with islet cell autotransplantation(TPIAT)is a viable treatment option upon failed endoscopic and medical therapy for patients with chronic pancreatitis.This procedure involves surgical removal of the entire pancreas,isolation of islet cells and reinfusion of these cells into the liver via portal vein[1,2].The risk of contamination to the final islet cell product can occur at several stages of the isolation procedure[3].In order to ensure the sterility of the islet cell product,multiple samples from the preservation and cannulation solution,and the final islet cell product are sent for bacterial cultures.Prior studies have found variable clinical consequences of these cultures on infectious com-plications or graft function[3-9].Herein we aimed to determine the incidence of infection in 60 days post-TPIAT and its association with the culture data.
基金Supported by the Project of Suzhou Hospital of Anhui Medical University,No.2020A1Natural Science Project of North Anhui Health Vocational College,No.WZK201907.
文摘Diabetes mellitus is a global health problem resulting from islet dysfunction or insulin resistance.The mechanisms of islet dysfunction are still under investigation.Islet hormone secretion is the main function of islets,and serves an important role in the homeostasis of blood glucose.Elucidating the detailed mechanism of islet hormone secretome distortion can provide clues for the treatment of diabetes.Therefore,it is crucial to develop accurate,real-time,laborsaving,high-throughput,automated,and cost-effective techniques for the sensing of islet secretome.Microfluidic chips,an elegant platform that combines biology,engineering,computer science,and biomaterials,have attracted tremendous interest from scientists in the field of diabetes worldwide.These tiny devices are miniatures of traditional experimental systems with more advantages of timesaving,reagent-minimization,automation,high-throughput,and online detection.These features of microfluidic chips meet the demands of islet secretome analysis and a variety of chips have been designed in the past 20 years.In this review,we present a brief introduction of microfluidic chips,and three microfluidic chipsbased islet hormone sensing techniques.We focus mainly on the theory of these techniques,and provide detailed examples based on these theories with the hope of providing some insights into the design of future chips or whole detection systems.
基金The study was approved by the Biomedical Research Ethics Committee of West China Hospital,Sichuan University(2014No.37).
文摘BACKGROUND Islet amyloid deposition and reducedβ-cell mass are pathological hallmarks in type 2 diabetes mellitus subjects.To date,the pathological features of the islets in diabetes secondary to pancreatic ductal adenocarcinoma(PDAC)have not been specifically addressed.AIM To provide further insight into the relationship between islet amyloid deposition of the residual pancreas in PDAC patients and to explore whether regional differences(proximal vs distal residual pancreas)are associated with islet amyloid deposition.METHODS We retrospectively collected clinical information and pancreatic tissue removed from tumors of 45 PDAC patients,including 14 patients with normal glucose tolerance(NGT),16 patients with prediabetes and 15 new-onset diabetes(NOD)patients diagnosed before surgery by an oral glucose tolerance test at West China Hospital from July 2017 to June 2020.Pancreatic volume was calculated by multiplying the estimated area of pancreatic tissue on each image slice by the interval between slices based on abdominal computer tomography scans.Several sections of paraffin-embedded pancreas specimens from both the proximal and/or distal regions remote from the tumor were stained as follows:(1)Hematoxylin and eosin for general histological appearance;(2)hematoxylin and insulin for the determination of fractionalβ-cell area(immunohistochemistry);and(3)quadruple insulin,glucagon,thioflavin T and DAPI staining for the determination ofβ-cell area,α-cell area and amyloid deposits.RESULTS Screening for pancreatic histologic features revealed that duct obstruction with islet amyloid deposition,fibrosis and marked acinar atrophy were robust in the distal pancreatic regions but much less robust in the proximal regions,especially in the prediabetes and NOD groups.Consistent with this finding,the remnant pancreatic volume was markedly decreased in the NOD group by nearly one-half compared with that in the NGT group(37.35±12.16 cm^(3) vs 69.79±18.17 cm^(3),P<0.001).As expected,islets that stained positive for amyloid(islet amyloid density)were found in the majority of PDAC cases.The proportion of amyloid/islet area(severity of amyloid deposition)was significantly higher in both prediabetes and NOD patients than in NGT patients(P=0.002;P<0.0001,respectively).We further examined the regional differences in islet amyloid deposits.Islet amyloid deposit density was robustly increased by approximately 8-fold in the distal regions compared with that in the proximal regions in the prediabetes and NOD groups(3.98%±3.39%vs 0.50%±0.72%,P=0.01;12.03%vs 1.51%,P=0.001,respectively).CONCLUSION In conclusion,these findings suggest that robust alterations of the distal pancreas due to tumors can disturb islet function and structure with islet amyloid formation,which may be associated with the pathogenesis of NOD secondary to PDAC.
基金Supported by the Juvenile Diabetes Research Foundation,No.4-2006-1025Diabetes Australia Research TrustTelethon Perth Children’s Hospital Research Fund(TPCHRF)grant to Jiang FX.
文摘A century has passed since the Nobel Prize winning discovery of insulin,which still remains the mainstay treatment for type 1 diabetes mellitus(T1DM)to this day.True to the words of its discoverer Sir Frederick Banting,“insulin is not a cure for diabetes,it is a treatment”,millions of people with T1DM are dependent on daily insulin medications for life.Clinical donor islet transplantation has proven that T1DM is curable,however due to profound shortages of donor islets,it is not a mainstream treatment option for T1DM.Human pluripotent stem cell derived insulin-secreting cells,pervasively known as stem cell-derivedβcells(SC-βcells),are a promising alternative source and have the potential to become a T1DM treatment through cell replacement therapy.Here we briefly review how isletβcells develop and mature in vivo and several types of reported SC-βcells produced using different ex vivo protocols in the last decade.Although some markers of maturation were expressed and glucose stimulated insulin secretion was shown,the SC-βcells have not been directly compared to their in vivo counterparts,generally have limited glucose response,and are not yet fully matured.Due to the presence of extra-pancreatic insulin-expressing cells,and ethical and technological issues,further clarification of the true nature of these SC-βcells is required.
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.
文摘目的探讨甘精胰岛素U300联合口服降糖药治疗2型糖尿病的临床效果。方法选择2021年10月—2023年1月广东省吴川市人民医院收治的79例2型糖尿病患者,随机分为非甘精组(39例)和U300组(40例)。非甘精组口服降糖药物治疗,在此之上,U300组增加甘精胰岛素U300治疗,持续治疗3个月,对比2组血糖及相关指标变化,并监测患者胰岛素功能相关指标改善情况,评估低血糖反应等不良反应情况。结果治疗后,U300组血糖指标、血糖波动指标均显著低于非甘精组,差异有统计学意义(P<0.05)。U300组治疗后胰岛素功能指标均显著优于非甘精组,空腹及餐后2 h C肽均显著高于非甘精组,差异有统计学意义(P<0.05)。U300组低血糖反应发生率(2.50%,1/40)和不良反应总发生率(20.00%,8/40)与非甘精组(2.56,1/39;17.95%,7/39)比较,差异无统计学意义(P>0.05)。结论增加甘精胰岛素U300治疗,可更好地提升患者血糖管理效果,并可改善胰岛功能,有利于稳定控制血糖,有助于提高患者病情控制效果,应用效果安全可靠。