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
To get recombinant antigen (Is/et Cell Autoantigen 69)ICA69 which was expressed in Escherichia coli strains (E.coli) by means of the gene engineering technique so that it can be used for early diagnosis of and screeni...To get recombinant antigen (Is/et Cell Autoantigen 69)ICA69 which was expressed in Escherichia coli strains (E.coli) by means of the gene engineering technique so that it can be used for early diagnosis of and screening in type Ⅰ diabetes mellitus, the cDNA fragment of human ICA69 was amplified by PCR, and then cloned into pSPORT 1 vector. After DNA sequencing, it was inserted into pGEX-2T between the sites of EcoR Ⅰ and Sma Ⅰ, then recombinant plasmid p2T-ICA69 was constructed and introduced into E.coli. The GST-ICA69 fusion protein was expressed by the induction of IPTG. The recombinant ICA69 proteins were used to detect the antibodies against hICA69 in 100 healthy subjects and type Ⅰ diabetic serum by the use of indirect ELISA. The sequence analysis showed that the amplified fragments contained 1449 bp, encoded 483 amino acids, and had been correctly inserted into pGEX-2T vector. The recombinant proteins expressed in the prokaryotic cells had immunogenicity and could be used to detect antibodies against ICA69 in type Ⅰ diabetic serum. Finally it can be concluded in this paper that the expression products obtained by the method of gene engineering are recombinant ICA69 antigen and may be used to improve the forecast rate and the diagnostic rate of type Ⅰ diabetes in combination with other tests.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
Type 1 diabetes mellitus is an autoimmune disease,which results in the permanent destruction of β-cells of the pancreatic islets of Langerhans.While exogenous insulin therapy has dramatically improved the quality of ...Type 1 diabetes mellitus is an autoimmune disease,which results in the permanent destruction of β-cells of the pancreatic islets of Langerhans.While exogenous insulin therapy has dramatically improved the quality of life,chronic diabetic complications develop in a substantial proportion of subjects and these complications generally progress and worsen over time.Although intensive insulin therapy has proven effective to delay and sometimes prevent the progression of complications such as nephropathy,neuropathy or retinopathy,it is difficult to achieve and maintain long term in most subjects.Reasons for this diff iculty include compliance issues and the increased risk of severe hypoglycemic episodes,which are generally associated with intensification of exogenous insulin therapy.Clinical studies have shown that transplantation of pancreas or purified pancreatic islets can support glucose homeostasis in type 1 diabetic patients.Islet transplantation carries the special advantages of being less invasive and resulting in fewer complications compared with the traditional pancreas or pancreas-kidney transplantation.However,islet transplantation efforts have limitations including the short supply of donor pancreata,the paucity of experienced islet isolation teams,side effects of immunosuppressants and poor long-term results.The purpose of this article is to review recent progress in clinical islet transplantation for the treatment of diabetes.展开更多
Islet cell transplantation has therapeutic potential to treat type 1 diabetes,which is characterized by autoimmune destruction of insulin-producing pancreatic isletβcells.It represents a minimal invasive approach for...Islet cell transplantation has therapeutic potential to treat type 1 diabetes,which is characterized by autoimmune destruction of insulin-producing pancreatic isletβcells.It represents a minimal invasive approach forβcell replacement,but long-term blood control is still largely unachievable.This phenomenon can be attributed to the lack of islet vasculature and hypoxic environment in the immediate post-transplantation period that contributes to the acute loss of islets by ischemia.Moreover,graft failures continue to occur because of immunological rejection,despite the use of potent immunosuppressive agents.Mesenchymal stem cells(MSCs)have the potential to enhance islet transplantation by suppressing inflammatory damage and immune mediated rejection.In this review we discuss the impact of MSCs on islet transplantation and focus on the potential role of MSCs in protecting islet grafts from early graft failure and from autoimmune attack.展开更多
BACKGROUND: Nonfunctioning islet cell tumor (NIT)as a rare pancreatic endocrine neoplasm is characterized byunspecific clinical symptoms and is hard to diagnose. InChina, NIT accounts for 15%-41% in pancreatic endocri...BACKGROUND: Nonfunctioning islet cell tumor (NIT)as a rare pancreatic endocrine neoplasm is characterized byunspecific clinical symptoms and is hard to diagnose. InChina, NIT accounts for 15%-41% in pancreatic endocrineneoplasms just next to insulinoma. In this study, weevaluated the surgical modalities of NIT.METHODS: From January 1978 through February 2002, 41patients with NIT were treated at the Department of Sur-gery of the First Affiliated Hospital, China Medical Univer-sity, Shenyang, China. Tumors in the head of the pancreaswere noted in 28 patients, and in the body or in the tail in13 patients. The mean diameter of the tumors was 10. 7cm. Fifteen patients underwent enucleation and 21 receivedpancreatectomy. Tumors were unresectable in 5 patientsbecause of extensive infiltration. The mean diameter was9.6 cm in patients treated by enucleation, 13.1 cm in thoseby pancreaticoduodenectomy, 9.9 cm in those by distalpancreatectomy, and 11.6 cm in those with unresectabletumors.RESULTS: The curative resection rate was 88% (n =36),and the complication rate after enucleation and pancreatec-tomy was 33% ( n = 5 ) and 14% (n=3), respectively. Nolocal recurrence was found after both enucleation and pan-createctomy. Liver metastases occurred in 3 patients treatedby enucleation.CONCLUSIONS: Both enucleation and pancreatectomy areeffective for NIT of the pancreas. No local recurrence hasbeen found in patients treated by the two surgical proce-dures. The complication rates of the two modalities arecomparable.展开更多
BACKGROUND: Triptolide (TPT) is a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook. F. It exhibits potent immunosuppressive and anti-inflammatory properties. This study was undertaken...BACKGROUND: Triptolide (TPT) is a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook. F. It exhibits potent immunosuppressive and anti-inflammatory properties. This study was undertaken to investigate its effects on prolongation of islet allograft survival in rodents. Additionally, we investigated whether TPT would be toxic to islet function in vivo. METHODS: We transplanted BALB/c islets to either chemically induced diabetic C57BL/6 mice or spontaneously diabetic non-obese diabetic (NOD) mice. TPT was injected within 2 weeks or continuously, until rejection, in the two combinations. Then, we evaluated the toxicity of TPT on islet function by daily injection to naive BALB/c or diabetic BALB/c that was cured by syngeneic islet transplantation under the kidney capsule. Mice injected with cyclosporine A (CsA) or vehicle served as controls. Intraperitoneal glucose tolerance tests (IPGTTs) performed at 4 and 8 weeks in the naive BALB/c group, and at 2, 4, 6, and 8 weeks in the syngeneic transplanted group. RESULTS: The medium survival time of islets allograft from TPT treated C57BL/6 and NOD recipients were 28.5 days (range 24-30 days, n=10) and 33.0 days (range 15-47 days, n=6), respectively, and they were significantly different from those of the vehicle treated controls, which were 14.0 days (range 13-16 days, n=6) and 5.0 days (range 4-10 days, n=6), respectively (all P<0.0001). The IPGTT demonstrated that there was no difference between the TPT treated and vehicle treated groups, either in the normal or syngeneic transplanted islet BALB/c mice. However, CsA injection impaired islet function in both normal and syngeneic transplanted mice as early as 4 weeks. CONCLUSION: TPT prolonged islets allograft survival in a chemically induced diabetic or an autoimmune diabetic murine model without impairment of islet function. (Hepatobiliary Pancreat Dis Int 2010; 9: 312-318)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
Intraportal transplantation of islets is no longer considered to be an ideal procedure and finding the extrahepatic alternative site is becoming a subject of high priority. Herein, in this study, we would introduce ou...Intraportal transplantation of islets is no longer considered to be an ideal procedure and finding the extrahepatic alternative site is becoming a subject of high priority. Herein, in this study, we would introduce our initial outcomes of using gastric submucosa（GS） and liver as sites of islet autotransplantation in pancreatectomized diabetic Beagles. Total pancreatectomy was performed in Beagles and then their own islets extracted from the excised pancreas were transplanted into GS（GS group, n=8） or intrahepatic via portal vein（PV group, n=5）. Forty-eight hours post transplantation, graft containing tissue harvested from the recipients revealed the presence of insulin-positive cells. All recipients in GS group achieved euglycemia within 1 day, but returned to a diabetic state at 6 to 8 days post-transplantation（mean survival time, 7.16±0.69 days）. However, all of the animals kept normoglycemic until 85 to 155 days post-transplantation in PV group（mean survival time, 120±28.58 days; P〈0.01 vs. GS group）. The results of intravenous glucose tolerance test（IVGTT） confirmed that the marked improvement in glycometabolism was obtained in intrahepatic islet autotransplantation. Thus, our findings indicate that the liver is still superior to the GS as the site of islet transplantation, at least in our islet autotransplant model in pancreatectomized diabetic Beagles.展开更多
Islet transplantation could become an ideal treatment for severe diabetes to prevent hypoglycemia shock and irreversible diabetic complications, once some of the major and unresolved obstacles are overcome, including ...Islet transplantation could become an ideal treatment for severe diabetes to prevent hypoglycemia shock and irreversible diabetic complications, once some of the major and unresolved obstacles are overcome, including limited donor supplies and side effects caused by permanent immunosuppressant use. Approximately 30 years ago, some groups succeeded in improving the blood glucose of diabetic animals by transplanting encapsulated islets with semi-permeable membranes consisting of polymer. A semi-permeable membrane protects both the inner islets from mechanical stress and the recipient’s immune system (both cellular and humoral immunities), while allowing bidirectional diffusion of nutrients, oxygen, glucose, hormones and wastes, i.e., immune-isolation. This device, which enables immune-isolation, is called encapsulated islets or bio-artificial pancreas. Encapsulation with a semipermeable membrane can provide some advantages: (1) this device protects transplanted cells from the recipient’s immunity even if the xenogeneic islets (from large animals such as pig) or insulin-producing cells are derived from cells that have the potential for differentiation (some kinds of stem cells). In other words, the encapsulation technique can resolve the problem of limited donor supplies; and (2) encapsulation can reduce or prevent chronic administration of immunosuppressants and, therefore, important side effects otherwise induced by immunosuppressants. And now, many novel encapsulated islet systems have been developed and are being prepared for testing in a clinical setting.展开更多
Objective To explore the mechanisms of differentiation and development of pancreatic endocrine cells as well as pancreatic regeneration.Methods Human embryonic pancreatic tissue at 7-14 weeks of gestation was collecte...Objective To explore the mechanisms of differentiation and development of pancreatic endocrine cells as well as pancreatic regeneration.Methods Human embryonic pancreatic tissue at 7-14 weeks of gestation was collected.Diabetes mellitus rat model was induced with 65 mg/kg of streptozotocin.Insulin, glucagon, somatostatin, nestin, and cytokeratin 19 (CK19) of pancreatic tissues were observed by immunohistochemistry.Results At 9 weeks of gestation, pancreatic epithelial cells began to co-express insulin, glucagon, somatostatin, and CK19 before migration.Islet cells gradually congregated along with the increase of aging, and at 14 weeks of gestation histological examination showed islet formation.At 12 weeks of gestation, nestin-positive cells could be seen in the pancreatic mesenchyme.During early embryogenesis, islet cells of pancreatic ducts co-expressed insulin, glucagon, and somatostatin.During pancreatic regeneration after damage, nestin expression of islet cells increased.Conclusion In the early stage of embryogenesis, islet cells of primary pancreatic ducts can be differentiated to multipotential endocrine cells before migration.During tissue regeneration, pancreatic stem cells may differentiate and proliferate to form pancreatic islet.展开更多
To isolate and culture the porcine pancreatic stem cells and investigate their function, the fetal porcine pancreatic stem cells were isolated by the method of suspending plus adhering culture. The isolated cells were...To isolate and culture the porcine pancreatic stem cells and investigate their function, the fetal porcine pancreatic stem cells were isolated by the method of suspending plus adhering culture. The isolated cells were then identified by immunohistochemical staining, and their culture viability measured through the MTT method in vitro. This induced them to differentiate into endocrine cells and detect their function. The isolated IPSCS did not express nestin, but expressed CK-19, a marker of ductal epithelia cells and ct-actin, a smooth muscle marker, demonstrating the growth characteristics of ES-like cells, and strong proliferative ability, after 18 passages. They could excrete insulin, and showed ultrastructure changes after being induced. Porcine pancreatic stem cells can be isolated by this method, induced to form islet-like clusters, and can secret insulin.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To get recombinant antigen (Is/et Cell Autoantigen 69)ICA69 which was expressed in Escherichia coli strains (E.coli) by means of the gene engineering technique so that it can be used for early diagnosis of and screening in type Ⅰ diabetes mellitus, the cDNA fragment of human ICA69 was amplified by PCR, and then cloned into pSPORT 1 vector. After DNA sequencing, it was inserted into pGEX-2T between the sites of EcoR Ⅰ and Sma Ⅰ, then recombinant plasmid p2T-ICA69 was constructed and introduced into E.coli. The GST-ICA69 fusion protein was expressed by the induction of IPTG. The recombinant ICA69 proteins were used to detect the antibodies against hICA69 in 100 healthy subjects and type Ⅰ diabetic serum by the use of indirect ELISA. The sequence analysis showed that the amplified fragments contained 1449 bp, encoded 483 amino acids, and had been correctly inserted into pGEX-2T vector. The recombinant proteins expressed in the prokaryotic cells had immunogenicity and could be used to detect antibodies against ICA69 in type Ⅰ diabetic serum. Finally it can be concluded in this paper that the expression products obtained by the method of gene engineering are recombinant ICA69 antigen and may be used to improve the forecast rate and the diagnostic rate of type Ⅰ diabetes in combination with other tests.
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.
基金Supported by The All Saints Health Foundation (in part)
文摘Type 1 diabetes mellitus is an autoimmune disease,which results in the permanent destruction of β-cells of the pancreatic islets of Langerhans.While exogenous insulin therapy has dramatically improved the quality of life,chronic diabetic complications develop in a substantial proportion of subjects and these complications generally progress and worsen over time.Although intensive insulin therapy has proven effective to delay and sometimes prevent the progression of complications such as nephropathy,neuropathy or retinopathy,it is difficult to achieve and maintain long term in most subjects.Reasons for this diff iculty include compliance issues and the increased risk of severe hypoglycemic episodes,which are generally associated with intensification of exogenous insulin therapy.Clinical studies have shown that transplantation of pancreas or purified pancreatic islets can support glucose homeostasis in type 1 diabetic patients.Islet transplantation carries the special advantages of being less invasive and resulting in fewer complications compared with the traditional pancreas or pancreas-kidney transplantation.However,islet transplantation efforts have limitations including the short supply of donor pancreata,the paucity of experienced islet isolation teams,side effects of immunosuppressants and poor long-term results.The purpose of this article is to review recent progress in clinical islet transplantation for the treatment of diabetes.
文摘Islet cell transplantation has therapeutic potential to treat type 1 diabetes,which is characterized by autoimmune destruction of insulin-producing pancreatic isletβcells.It represents a minimal invasive approach forβcell replacement,but long-term blood control is still largely unachievable.This phenomenon can be attributed to the lack of islet vasculature and hypoxic environment in the immediate post-transplantation period that contributes to the acute loss of islets by ischemia.Moreover,graft failures continue to occur because of immunological rejection,despite the use of potent immunosuppressive agents.Mesenchymal stem cells(MSCs)have the potential to enhance islet transplantation by suppressing inflammatory damage and immune mediated rejection.In this review we discuss the impact of MSCs on islet transplantation and focus on the potential role of MSCs in protecting islet grafts from early graft failure and from autoimmune attack.
文摘BACKGROUND: Nonfunctioning islet cell tumor (NIT)as a rare pancreatic endocrine neoplasm is characterized byunspecific clinical symptoms and is hard to diagnose. InChina, NIT accounts for 15%-41% in pancreatic endocrineneoplasms just next to insulinoma. In this study, weevaluated the surgical modalities of NIT.METHODS: From January 1978 through February 2002, 41patients with NIT were treated at the Department of Sur-gery of the First Affiliated Hospital, China Medical Univer-sity, Shenyang, China. Tumors in the head of the pancreaswere noted in 28 patients, and in the body or in the tail in13 patients. The mean diameter of the tumors was 10. 7cm. Fifteen patients underwent enucleation and 21 receivedpancreatectomy. Tumors were unresectable in 5 patientsbecause of extensive infiltration. The mean diameter was9.6 cm in patients treated by enucleation, 13.1 cm in thoseby pancreaticoduodenectomy, 9.9 cm in those by distalpancreatectomy, and 11.6 cm in those with unresectabletumors.RESULTS: The curative resection rate was 88% (n =36),and the complication rate after enucleation and pancreatec-tomy was 33% ( n = 5 ) and 14% (n=3), respectively. Nolocal recurrence was found after both enucleation and pan-createctomy. Liver metastases occurred in 3 patients treatedby enucleation.CONCLUSIONS: Both enucleation and pancreatectomy areeffective for NIT of the pancreas. No local recurrence hasbeen found in patients treated by the two surgical proce-dures. The complication rates of the two modalities arecomparable.
文摘BACKGROUND: Triptolide (TPT) is a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook. F. It exhibits potent immunosuppressive and anti-inflammatory properties. This study was undertaken to investigate its effects on prolongation of islet allograft survival in rodents. Additionally, we investigated whether TPT would be toxic to islet function in vivo. METHODS: We transplanted BALB/c islets to either chemically induced diabetic C57BL/6 mice or spontaneously diabetic non-obese diabetic (NOD) mice. TPT was injected within 2 weeks or continuously, until rejection, in the two combinations. Then, we evaluated the toxicity of TPT on islet function by daily injection to naive BALB/c or diabetic BALB/c that was cured by syngeneic islet transplantation under the kidney capsule. Mice injected with cyclosporine A (CsA) or vehicle served as controls. Intraperitoneal glucose tolerance tests (IPGTTs) performed at 4 and 8 weeks in the naive BALB/c group, and at 2, 4, 6, and 8 weeks in the syngeneic transplanted group. RESULTS: The medium survival time of islets allograft from TPT treated C57BL/6 and NOD recipients were 28.5 days (range 24-30 days, n=10) and 33.0 days (range 15-47 days, n=6), respectively, and they were significantly different from those of the vehicle treated controls, which were 14.0 days (range 13-16 days, n=6) and 5.0 days (range 4-10 days, n=6), respectively (all P<0.0001). The IPGTT demonstrated that there was no difference between the TPT treated and vehicle treated groups, either in the normal or syngeneic transplanted islet BALB/c mice. However, CsA injection impaired islet function in both normal and syngeneic transplanted mice as early as 4 weeks. CONCLUSION: TPT prolonged islets allograft survival in a chemically induced diabetic or an autoimmune diabetic murine model without impairment of islet function. (Hepatobiliary Pancreat Dis Int 2010; 9: 312-318)
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.
基金supported by the Postdoctoral Science Foundation of China(No 2015M582853)the Natural Science Foundation of Tianjin,China(No.13JCYBJC42600)
文摘Intraportal transplantation of islets is no longer considered to be an ideal procedure and finding the extrahepatic alternative site is becoming a subject of high priority. Herein, in this study, we would introduce our initial outcomes of using gastric submucosa（GS） and liver as sites of islet autotransplantation in pancreatectomized diabetic Beagles. Total pancreatectomy was performed in Beagles and then their own islets extracted from the excised pancreas were transplanted into GS（GS group, n=8） or intrahepatic via portal vein（PV group, n=5）. Forty-eight hours post transplantation, graft containing tissue harvested from the recipients revealed the presence of insulin-positive cells. All recipients in GS group achieved euglycemia within 1 day, but returned to a diabetic state at 6 to 8 days post-transplantation（mean survival time, 7.16±0.69 days）. However, all of the animals kept normoglycemic until 85 to 155 days post-transplantation in PV group（mean survival time, 120±28.58 days; P〈0.01 vs. GS group）. The results of intravenous glucose tolerance test（IVGTT） confirmed that the marked improvement in glycometabolism was obtained in intrahepatic islet autotransplantation. Thus, our findings indicate that the liver is still superior to the GS as the site of islet transplantation, at least in our islet autotransplant model in pancreatectomized diabetic Beagles.
基金Supported by Research Seeds Quest Program in Japan Science and Technology Agency (NS)the Uehara Memorial Foundation (NS)Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports Science and Technology of Japan, B: 22390253 (SE), C: 22591513 (NS)
文摘Islet transplantation could become an ideal treatment for severe diabetes to prevent hypoglycemia shock and irreversible diabetic complications, once some of the major and unresolved obstacles are overcome, including limited donor supplies and side effects caused by permanent immunosuppressant use. Approximately 30 years ago, some groups succeeded in improving the blood glucose of diabetic animals by transplanting encapsulated islets with semi-permeable membranes consisting of polymer. A semi-permeable membrane protects both the inner islets from mechanical stress and the recipient’s immune system (both cellular and humoral immunities), while allowing bidirectional diffusion of nutrients, oxygen, glucose, hormones and wastes, i.e., immune-isolation. This device, which enables immune-isolation, is called encapsulated islets or bio-artificial pancreas. Encapsulation with a semipermeable membrane can provide some advantages: (1) this device protects transplanted cells from the recipient’s immunity even if the xenogeneic islets (from large animals such as pig) or insulin-producing cells are derived from cells that have the potential for differentiation (some kinds of stem cells). In other words, the encapsulation technique can resolve the problem of limited donor supplies; and (2) encapsulation can reduce or prevent chronic administration of immunosuppressants and, therefore, important side effects otherwise induced by immunosuppressants. And now, many novel encapsulated islet systems have been developed and are being prepared for testing in a clinical setting.
文摘Objective To explore the mechanisms of differentiation and development of pancreatic endocrine cells as well as pancreatic regeneration.Methods Human embryonic pancreatic tissue at 7-14 weeks of gestation was collected.Diabetes mellitus rat model was induced with 65 mg/kg of streptozotocin.Insulin, glucagon, somatostatin, nestin, and cytokeratin 19 (CK19) of pancreatic tissues were observed by immunohistochemistry.Results At 9 weeks of gestation, pancreatic epithelial cells began to co-express insulin, glucagon, somatostatin, and CK19 before migration.Islet cells gradually congregated along with the increase of aging, and at 14 weeks of gestation histological examination showed islet formation.At 12 weeks of gestation, nestin-positive cells could be seen in the pancreatic mesenchyme.During early embryogenesis, islet cells of pancreatic ducts co-expressed insulin, glucagon, and somatostatin.During pancreatic regeneration after damage, nestin expression of islet cells increased.Conclusion In the early stage of embryogenesis, islet cells of primary pancreatic ducts can be differentiated to multipotential endocrine cells before migration.During tissue regeneration, pancreatic stem cells may differentiate and proliferate to form pancreatic islet.
文摘To isolate and culture the porcine pancreatic stem cells and investigate their function, the fetal porcine pancreatic stem cells were isolated by the method of suspending plus adhering culture. The isolated cells were then identified by immunohistochemical staining, and their culture viability measured through the MTT method in vitro. This induced them to differentiate into endocrine cells and detect their function. The isolated IPSCS did not express nestin, but expressed CK-19, a marker of ductal epithelia cells and ct-actin, a smooth muscle marker, demonstrating the growth characteristics of ES-like cells, and strong proliferative ability, after 18 passages. They could excrete insulin, and showed ultrastructure changes after being induced. Porcine pancreatic stem cells can be isolated by this method, induced to form islet-like clusters, and can secret insulin.
