ABSTRACT
Objective:To explore the protective effect of methyl eugenol (Me) on islet ischemia/reperfusion (I/R) injury and elucidate its underlying mechanism.Methods:The islets were isolated and purified from 6-8 week male BALB/c mice and divided into four groups of normal control (normal culture without any treatment), hypoxia/reoxygenation (H/R treatment), H/R+ dimethyl sulfoxide (DMSO dosing plus H/R treatment) and H/R+ Me (Me dosing plus H/R). Viability of islet cells in each group was detected by acridine orange (AO)/propidium iodide (PI) double stain.Function of islet cells (insulin secretion) was measured by enzyme-linked immunosorbent assay (ELISA). Murine islet β Min6 cells were selected for detecting the effect of Me on the proliferative activity of normal cultured and H/R treated islet cells under different concentration gradients by CCK8.Then Min6 cells were divided into four groups of normal, H/R, H/R+ DMSO and H/R+ Me.The definition of group was the same as that of primary murine islets.Flow cytometry and Hoechst 33342 nuclear stain were utilized for detecting cell apoptotic rate in each group.The protein expressions of p-JNK, p-p38, JNK, p38, Bcl-2 and Bax were detected by Western blot.And the data were processed by one-way ANOVA or t test.Results:The proportion of dead islet cells in H/R group was (29.47±2.65)% and it was significantly lower than that in normal group (7.63±1.53)%.And the inter-group differences were statistically significant ( P<0.001). The proportion of dead islet cells was (20.63±3.07)% in H/R+ Me group.It was higher than that in H/R group (29.47±2.65)% and in H/R+ DMSO group (30.13±1.50)% and inter-group difference was statistically significant ( P<0.05 & P<0.01). Under the stimulation of high glucose, the insulin secretion level of islet in H/R+ Me group was (1.76+ 0.08) mg/L, which was higher than that in H/R group and H/R+ DMSD group(1.24±0.14)mg/L and(1.27±0.05)mg/L, and the difference was statistically significant[(1.76±0.08) vs. (1.24±0.14) mg/L; (1.76±0.08) vs.(1.27±0.05) mg/L, P<0.01]. There was no significant effect on cell viability after Me dosing within a certain concentration range (0-40 μmol/L). After Me dosing (5 μmol/L), cell viability of H/R-treated Min6 cells was significantly higher than that without Me.And the difference was statistically significant[(1.19±0.03) vs.(1.00±0), P<0.01]. As compared with H/R and H/R+ DMSO groups, overall apoptotic rate declined in H/R+ Me group (Hoechst 33342 stain: 14.50%±1.05% vs. 23.30%±1.18%, 14.50%±1.05% vs. 22.77%±1.75%, P<0.001; Flow cytometry: 4.36%±0.54% vs. 21.44%±1.02%, 4.36%±0.54% vs. 21.68%±3.06%, P<0.01). The expressions of p-JNK and p-p38 were down-regulated (p-JNK: 0.77±0.06 vs. 1.03±0.05, 0.77±0.06 vs.0.93±0.04, P<0.001; p-p38: 0.80±0.05 vs. 1.01±0.08; 0.80±0.05 vs. 1.00±0.05, P<0.05) while Bcl-2/Bax ratio rose (1.62±0.13 vs. 0.72±0.10, 1.62±0.13 vs. 0.74±0.13, P<0.01). Conclusions:Me can improve the viability and function of islets and suppress the apoptosis of Min6 cells after H/R.The mechanism is correlated with JNK and p38 MAPK signaling pathways.
ABSTRACT
Objective:To investigate the clinical efficacy of modified Bingtitang in treatment of type 2 diabetes mellitus(T2DM) and its effect on pancreas islet function. Method:A total of 108 patients with T2DM were divided into two groups according to the digital number table method, with 54 cases in each group. The control group were given routine therapy of diabetic diet, proper exercise and blood sugar control, while the treatment group were orally given traditional Chinese medicine (TCM) and modified Bingtitang in addition to the therapy of the control group. The blood sugar, pancreas islet function-related indexes, TCM syndrome score, serum retinol binding protein 4 (RBP4) and Betatrohin levels were compared between two groups before and after treatment. The total effective rate was also compared. Result:After treatment, the fasting blood glucose (FPG), glycated hemoglobin (HbA1c), blood glucose variation coefficient (CV-FPG), insulin resistance index (HOMA-IR) of the treatment group were lower than those of control group (PΔI30/ΔG30)of treatment group were higher than those of the control group (PPPPConclusion:In addition to the routine treatment, modified Bingtitang can effectively control blood sugar, improve pancreas islet function, and alleviate TCM syndromes, with a significant effect on T2DM. Its mechanism may be related to the regulation of serum RBP4 and Betatrohin levels.
ABSTRACT
This study investigated the abnormal expression of ATP synthase β-subunit (ATPsyn-β) in pancreas islets of rat model of polycystic ovary syndrome (PCOS) with type 2 diabetes mellitus (T2DM),and the secretion function changes after up-regulation of ATP5b.Sixty female SD rats were divided into three groups randomly and equally.The rat model of PCOS with T2DM was established by free access to the high-carbohydrate/high-fat diet,subcutaneous injections of DHEA,and a single injection of streptozotocin.The pancreas was removed for the detection of the ATPsyn-β expression by immunohistochemical staining,Western blotting and reverse transcription-PCR (RT-PCR).The pancreas islets of the rats were cultured,isolated with collagenase Ⅴ and purified by gradient centrifugation,and the insulin secretion after treatment with different glucose concentrations was tested.Lentivirus ATP5b was successfully constructed with the vector of GV208 and transfected into the pancreas islets for the over-expression of ATPsyn-β.The insulin secretion and intracellular ATP content were determined after transfection of the PCOS-T2DM pancreas islets with Lenti-ATP5b.The results showed that the expression of ATPsyn-β protein and mRNA was significantly decreased in the pancreas of PCOS-T2DM rats.The ATP content in the pancreas islets was greatly increased and the insulin secretion was improved after the up-regulation of ATPsyn-β in the pancreas islets transfected with lenti-ATP5b.These results indicated that for PCOS,the ATPsyn-β might be one of the key factors for the attack of T2DM.
ABSTRACT
Objective To investigate the effects on pancreas islet function in patients ubdergoing laparoscopic myomectomy during sevoflurane or propofol anesthesia.Methods Forty pa-tients,40-55 years,ASA Ⅰ or Ⅱ scheduled for elective surgery of laparoscopic myomectomy were randomly divided into two groups (n=20 each group).Propofol 2 mg/kg,sufentanil 0.5 μg/kg and rocuronium 0.9 mg/kg were used for induction,BIS was controlled between 40 and 55 during surgery.The anesthesia was maintained with sevoflurane and MAC was maintained with 0.7-1.3 in group S.The anesthesia was maintained with propofol continuous infusion and the plasma concentra-tion of target was set between 2.0 to 5.0μg/ml in group P.Blood glucose,insulin,c-peptide,gluca-gon and cortisol were measured at 3 time points:before induction of anesthesia (T0 ),start of surgery (T1 ),end of surgery(T2 ).Results Compared with T0 ,blood glucose,insulin,c-peptide,glucagon and cortisol in two groups were increased significantly at T1 and T2 (P <0.05).Compared with T1 , blood glucose,insulin,c-peptide,glucagon and cortisol in two groups were increased significantly at T2 (P <0.05).Compared with group S,blood glucose,glucagon and cortisol were increased indis-tinctively and insulin,c-peptide were increased significantly in group P at T1 and T2 (P < 0.05). Conclusion Compared with sevoflurane,propofol could promote the secretion of insulin and c-pep-tide,and inhibit cortisol and glucagon secretion,thus inhibit the rise of intraoperative blood glucose.
ABSTRACT
Diabetes is in the category ofin TCM, which is mainly discussed in light ofdeficiency. The conception vessel is the sea ofmeridians, acting on regulating the accumulation and irrigation ofand blood of twelve meridians and collaterals. The physiological function of the conception vessel is closely related to the pathogenesis of, its running course is highly coincident with the location ofand the symptoms ofare relevant with the indications of the conception vessel. Hence, harmonizingand blood of the conception vessel may be an effective approach to the prevention and treatment of.
ABSTRACT
Objective To study the effect and mechanism of gastric bypass surgery on type 2 diabetic rats.Methods The models of type 2 diabetic rats were induced by stretozotocin and 20 diabetic rats were randomly divided into 2 groups:diabetes-operation group (DO group,n =10)and diabetes-control group(DC group,n =10).20 normal rats were randomly divided into 2 groups:normal-operation(NO group,n =10) and normalcontrol group(NC group,n =10).Rats in DO and NO group underwent GBP and rats in DC group and NC group underwent sham operation.Fasting blood glucose(FBG) levels of rats in each group were detected before operation and on 72 h,1th week,4th week,8th week after operation.On the 8th week after operation,pancreas tissues were harvested for HE staining and immunofluorescence,histological changes observed.Results The FBG levels of rats were not statistically significant different before operation between DO group and DC group or between NO group and NC group (P ＞ 0.05).After operation,the FBG levels of rats in DO group gradually declined (P ＜ 0.05).FBG levels of rats in DO group were lower after operation than before operation(P ＜0.05) ; After operation FBG levels of rats were higher in DO group than in NO group and NC group at the same time point (P ＜0.05).In DC group,the difference of FBG levels of rats at different time point was not statistically significant(P ＞ 0.05).The difference of FBG had no statistically significance between the different time points of the same group or between the same time point of different groups (P ＞ 0.05).HE staining showed that,in DO group,newborn small islets appeared in pancreas which increased the number of islet.The new islets were smaller,mostly around the pancreatic duct and the structure was similar to that of the normal islets.Immunofluorescence staining also showed that the number of islets increased.Insulin immunofluorescence found more isolated small islets composed of two or three insulin positive cells.Insulin and glucagon double immunofluorescence found insulin and glucagon double positive(INS +/GLU +)cells in some islets.Conclusions GBP has obvious hypoglycemic effects on FBG levels of type 2 diabetic rats,in which the regeneration of pancreas islets may play an important role,while on normal rats GBP has no hypoglycemic effects.
ABSTRACT
Objective To determine the molecular pathway of reconstituted basement membrane extract(BME)embedment in the context of promoting islet cell survival.Methods Mouse islet cells were isolated and embedded in BME for in vitro culture.Caspase-3,integrin-α1 and 5,PDX-1,Akt,FAK and phospho Erk were detected using Western blot.Results Islet cells embedded with BME were partially protected from apoptosis indicated by a lower caspase-3 level and an increased phosphoAkt activity compared with untreated control.In addition,an increase of α3-integrin,FAK protein level and FAK activity were observed as well.Furthermore,the expression of PDX-1 and phosphoErk at the 48 h mark were preserved,suggesting the positive effect of BME to islet activity.Conclusion These results indicate that the embedment of BME construction can up-regulate α3 integrin and its signal transduction,which may improve viability and function of islet cells.
ABSTRACT
Objective To evaluate the effects of carbohydrate-electrolyte solution(CES)on serum glucose,pancreas islet function,and safety in elderly patients after abdominal operation.Methods In this prospective,double-blinded,randomized,and controlled study,40 elderly patients who met the defined criteria were enrolled.Subjects in CES group were intravenously administered with 1 000 ml CES for consecutive three days beginning from the 1st and 2nd post-operative day,while subjects in the control group were administered with 10% glucose of the same volume under the same arrangement.The changes of serum glucose,insulin and insulin C-peptide,as well as lactic acid and uric acid and uric acid were determined before and after injection.Adverse events were recorded.Results All patients completed the study.The increase rate of serum glucose was significantly lower on the 2nd and 3rd day after injection in CES group than in control group(P=0.008,P:0.001).Blood insulin and insulin C-peptide levels showed increasing trends in both two groups,but were not significantly different between two groups(P=0.612,P=0.213).In the CES group,6 patients experienced systemic inflammatory response syndrome and 4 patients had infective complications after surgeries ;on the contrary,these two numerals were 8 and 6 in the control group(P=0.639,P=0.606).No increase in serum lactic acid or uric acid was detected.Conclusion Appropriate application of CES has minimal effect on the blood gluocse and pancreas islet function in elderly patients after abdominal surgery and may be helpful to improve clinical outcomes.
ABSTRACT
Islet transplantation had been suggested as a potential treatment modality for type I diabetes mellitus for the last two decades. The methods for the islet isolation and purification were developed. In 2000, the excellent clinical outcomes from the Edmonton group were reported. And various basic researches were performed for the elucidation of the mechanism of initial islet loss. Although the Edmonton protocol, which had initially raised hopes that all the technical and immunologic problems would be solved, recently revealed as a limited success within the selective cases and short-term follow-up, these inspirations led us to the subsequent clinical or basic research of islet transplantation. As a result, many clinical trials and studies have been attempted for the establishment of the optimal immune suppression regimen, the prevention from islet loss in the process of isolation, and the improvement of the intraportal engraftment. This article reviews the history and the recent progress and possible strategies for the clinical islet transplantation.
Subject(s)
Diabetes Mellitus , Hope , Islets of Langerhans TransplantationABSTRACT
Pancreas islet cell transplantation has been regarded as an ideal method to treat the type I diabetes mellitus. However, it could not be the method of choice because of poor graft survival rate after transplantation. Recently, the outcome of pancreas islet cell transplantation has been improving, especially since the Edmonton group has succeeded in controlling the glucose metabolism in 7 consecutive type I diabetes mellitus patients. Returning to diabetic status in a substantial portion of transplanted patients, however, has revealed that lots of hurdles, such as primary non-function of the islet from non-specific inflammation, immunologic destruction of islets from either allogenic or autoimmune process, and shortage of donor source, remained to be solved in the near future, if pancreas islet cell transplantation is to be a practical clinical treatment modality for diabetic patients. We herein discuss on the current status and future of pancreas islet cell transplantation.
Subject(s)
Humans , Diabetes Mellitus , Glucose , Graft Survival , Inflammation , Islets of Langerhans , Metabolism , Pancreas , Tissue Donors , TransplantationABSTRACT
PURPOSE: Islet cell transplantation, as an alternative approach to endocrine cell replacement to treat the diabetes mellitus, has received significant attention because it holds several advantages over whole gland transplantation. However cell damage from islet isolation and immunologic rejection after transplantation prevent from successful clinical application for diabetic patients. Culture of cells at low temperature has known to stabilize the cell viability, and to decrease the immunologic antigenicity. Aim of this study is to investigate the effect of culture at 24oC on cell viability, cellular function, immunogenicity and cytokine profiles in rat pancreas islet. METHODS: Pancreas islets were isolated from Lewis rat and cultured at 24oC or 37oC during 14 days. Islet recovery after culture period was counted as islet equivalent number, and islet viability was examined with fluorescent vital staining (FDA/PI). Islet function was measured with glucose stimulation test. Annexin V expression and MHC class I and II expression were measured with flow cytometric assay for apoptosis and immunogenicity respectively. Lymphocyte cell proliferation through mixed lymphocyte islet culture was examined with WST-1 proliferation assay. Cytokine profiles were analyzed with quantitative real time RT-PCR. All these parameters were measured on 1, 3, 5, 7, 14 culture days after islet isolation. RESULTS: Islet recovery was higher in islet cultured at 24oC than in islet cultured at 37oC without change of viability. Insulin secretion after glucose stimulation was more effective in 24oC culture condition. Decrease of apoptotic cell death was demonstrated in 24oC cultured islet. MHC class I and II expression on islets and lymphocyte proliferation when cocultured with islets were less prominent in 24oC cultured islet. TNF-alpha and IL-4 cytokine expression was higher in islet cultured at 24oC than in islet cultured at 37oC. IL-1beta and IL-10 cytokine expression were similar in both culture condition. CONCLUSION: This study demonstrated that cell recovery and function are increased in islet cultured at 24oC than in islet cultured at 37oC while antigenicity and proinflammatory cytokine expression are decreased. Low temperature culture can be a good approach to prevent the loss of islet mass, and to reduce the immunologic rejection of transplanted islet for successful clinical islet transplantation.
Subject(s)
Animals , Humans , Rats , Annexin A5 , Apoptosis , Cell Death , Cell Proliferation , Cell Survival , Diabetes Mellitus , Endocrine Cells , Glucose , Insulin , Interleukin-10 , Interleukin-4 , Islets of Langerhans Transplantation , Islets of Langerhans , Lymphocytes , Pancreas , Tumor Necrosis Factor-alphaABSTRACT
Objective To evaluate the effect of FTY720 on pancreas islet xenograft rejection by setting up the rat-to-mouse islet xenotransplantation model. Methods Rat islets were harvesed by means of pancreatic duct irregution with collagenase and purified by discontinuous density gradient method. Then the islets were transplanted under the kidney capsule of the mouse. The recipients were divided into 3 groups randomly: control group,the mouth was administrated with saline without any immunosuppressant; experiment group 1,the mouth was administrated with FTY720 (1.0 mg/kg) orally from the operation day to day 14 after operation; experiment group 2,the mouth was administrated with combination of FTY720(1.0 mg/kg) with CsA(15 mg/kg) from the operation day to day14 after operation. The xenograft were removed with the kidney at day 3, 5, 7 and 14 after transplantation, and the rejection was analyzed. Results In the control group and experiment group 1, the xenografts were completely destroyed within one week; on day 7, no intact islets could be seen, but numerous lymphocytes infiltration were found. In experiment group 2, many intact islets were still seen under the kidney capsule in day7 and 14 after operation; and infiltrated lymphocytes could hardly or just occasionally be found. Conclusions FTY720 alone can not inhibit the rejection of islet xenotransplantation; FTY720 combination with CsA can inhibited islet xenograft rejection effectively in the rat-to-mouse model.
ABSTRACT
PURPOSE: Transplantation of pancreas islet has been worldwidely studied as a one of therapeutic modalities to achieve the insulin independence. We studied whether the expression of vascular endothelial growth factor (VEGF) on pancreas islets with liposomal VEGF gene transfer could improve the efficacy of early implantation and long term graft survival in pancreatic islet cell transplantation. METHODS: Syngenic pancreas islets were transplanted beneath the renal capsule. Islets were transfected with plasmid VEGF c-DNA using cationic liposome DMRIE-C. Glucose metabolism and histologic findings were compared between the groups transplanted with VEGF DNA containing islets (n=5) and the control group with (n=5) or without (n=4) local recombinant VEGF adminstration during islet transplant. RESULTS: Glucose was controlled at 5.5 days after transplantation in control group without r-VEGF adminstration, at 4 days in group with recombinant VEGF adminstration, and at 6.6 days in group with VEGF DNA transfected islets. Euglycemia was maintained over 150 days in control group. However, graft failure was developed in 22 days after transplantation in group with VEGF DNA transfected islet. Histologically there were severe infiltrations of neutrophil and lymphocyte in VEGF DNA transfected grafts from 5 days after transplantation. CONCLUSION: Although VEGF could be a favorable angiogenic factor in pancreas islet transplantation, VEGF expression following VEGF DNA transfection into islets could not increase the graft survival due to inflammatory process. More investigations are needed to clarify the mechanism on destructive process of islets after gene transfection into islets, and another approaches to get the effect of gene transfection should be followed.
Subject(s)
Angiogenesis Inducing Agents , Cell Transplantation , DNA , Endothelial Growth Factors , Glucose , Graft Survival , Insulin , Islets of Langerhans Transplantation , Islets of Langerhans , Liposomes , Lymphocytes , Metabolism , Neutrophils , Pancreas , Plasmids , Transfection , Transplants , Vascular Endothelial Growth Factor AABSTRACT
BACKGROUND: Transplantation of Pancreatic islet represents one of the most exciting treatment modalities for Type I diabetes mellitus. To achieve better graft survival, it is important to protect the graft from alloantigen-specific immune response. It was emphasized that islets, as with other forms of cellular transplants, have the potential advantage of being immunologically altered before transplantation, resulting in tolerance to the host without using long-term, nonspecific immunosuppression. The mixed islet-lymphocyte culture is an excellent tool to evaluate the immunogenicity of a pancreatic islets. Therefore, we co-cultured pancreatic islet and lymphocyte to investigate cytokine gene expression from the lymphocyte, and to investigate pancreatic islet viability and functional changes after co-culture. MATERIALS AND METHODS: Lewis rat islets were purified from pancreas by collagenase type XI and dextran gradient method. Afterwards, Lewis rat islets were co-cultured as a stimulator and Wistar rat lymphocyte as a reponder. As a control group lymphocyte alone and islet alone were cultured in a same condition. For estimating islets viability, we counted islet viability as an IEQ (Islet equivalent). For evaluation of islets function, insulin release assay was perfomed by RIA under the glucose challenge. used by RIA. We studied cytokines gene expression of cultured cells by reverse transcriptase polymerase chain reaction (RT-PCR). RESULT AND CONCLUSION: 1) Islet yield was 1229.8 420.1 per rat, and counted as 2615.4 548.2 IEQ per rat. 2) Islet viability was decreased gradually with the lapse of time, more rapid in allogenic co-culture group than islet alone or isogenic co-culture group. 3) Release of insulin increased until day 3, and then decreased gradually. Insulin release was positively correlated with glucose gradient. The amount of released insulin was greater in co-cultured group than islet alone group. 4) Interleukine-2 and interferron-gamma gene expression increased in allo co-culture group, however transforming growth factor-beta gene expression was not affected by co-culture.
Subject(s)
Animals , Rats , Cells, Cultured , Coculture Techniques , Collagenases , Cytokines , Dextrans , Diabetes Mellitus , Gene Expression , Glucose , Graft Survival , Immunosuppression Therapy , Insulin , Islets of Langerhans , Lymphocytes , Pancreas , Reverse Transcriptase Polymerase Chain Reaction , TransplantsABSTRACT
BACKGROUND: Transplantation of Pancreatic islet represents one of the most exciting treatment modalities for Type I diabetes mellitus. To achieve better graft survival, it is important to protect the graft from alloantigen-specific immune response. It was emphasized that islets, as with other forms of cellular transplants, have the potential advantage of being immunologically altered before transplantation, resulting in tolerance to the host without using long-term, nonspecific immunosuppression. The mixed islet-lymphocyte culture is an excellent tool to evaluate the immunogenicity of a pancreatic islets. Therefore, we co-cultured pancreatic islet and lymphocyte to investigate cytokine gene expression from the lymphocyte, and to investigate pancreatic islet viability and functional changes after co-culture. MATERIALS AND METHODS: Lewis rat islets were purified from pancreas by collagenase type XI and dextran gradient method. Afterwards, Lewis rat islets were co-cultured as a stimulator and Wistar rat lymphocyte as a reponder. As a control group lymphocyte alone and islet alone were cultured in a same condition. For estimating islets viability, we counted islet viability as an IEQ (Islet equivalent). For evaluation of islets function, insulin release assay was perfomed by RIA under the glucose challenge. used by RIA. We studied cytokines gene expression of cultured cells by reverse transcriptase polymerase chain reaction (RT-PCR). RESULT AND CONCLUSION: 1) Islet yield was 1229.8 420.1 per rat, and counted as 2615.4 548.2 IEQ per rat. 2) Islet viability was decreased gradually with the lapse of time, more rapid in allogenic co-culture group than islet alone or isogenic co-culture group. 3) Release of insulin increased until day 3, and then decreased gradually. Insulin release was positively correlated with glucose gradient. The amount of released insulin was greater in co-cultured group than islet alone group. 4) Interleukine-2 and interferron-gamma gene expression increased in allo co-culture group, however transforming growth factor-beta gene expression was not affected by co-culture.
Subject(s)
Animals , Rats , Cells, Cultured , Coculture Techniques , Collagenases , Cytokines , Dextrans , Diabetes Mellitus , Gene Expression , Glucose , Graft Survival , Immunosuppression Therapy , Insulin , Islets of Langerhans , Lymphocytes , Pancreas , Reverse Transcriptase Polymerase Chain Reaction , TransplantsABSTRACT
A case of 39-year-old diabetic patient with a calcitonin and somatostatin secreting pancreatic islet tumor is presented. He had suffered from chronic diarrhea and dyspepsia for 10 years and was diagnosed with diabetes 2 years ago. Abdominal CT revealed a huge abdominal mass which was considered as a neuroendocrine tumor after US-guided needle biopsy. A distal pancreatectomy and splenectomy were performed. Histologically, tumor cells, amanged in solid sheets, showed small nuclei without significant atypia and granular eosinophilic cytoplasm. Tumor cells showed strong immunoreacitivity for calcitonin and somatostatin. The serum clacitonin was markedly elevated (268.7 pmol/L, normal range; 0.9-7.6 pmol/L). After resection of the tumor, diarrhea and dyspepsia diappeared, and oral glucose tolerance test showed normal glucose tolerance with normalization of calcitonin.
Subject(s)
Adult , Humans , Biopsy, Needle , Calcitonin , Cytoplasm , Diabetes Mellitus , Diarrhea , Dyspepsia , Eosinophils , Glucose , Glucose Tolerance Test , Islets of Langerhans , Neuroendocrine Tumors , Pancreatectomy , Reference Values , Somatostatin , Splenectomy , Tomography, X-Ray ComputedABSTRACT
Purification of islets in pancreas islet cell transplantation has some potential advantages ,such as more safety, improved islet cell implantation, and reduced immunogenicity, compared with an unpurified pancreas islet cell transplantation. We evaluated the effect of islet cell purification on islet yields, hemodynamics, and graft outcome following intraportal canine pancreas islet cell transplantation. The baseline characteristics, including body weight, pancreas weight and collagenase recirculation time for the unpurified group(n=12) and the purified group(n=17) did not show any significant difference(P>0.05). The mean cell pellet volume before intraportal injection was 25.4 ml in the unpurified group and 7.2ml in the purified group(P0.05). Mean recovery rate of islet after purification was 66.8%. The portal pressure change after intraportal islet injection was significantly less in the purified group(16.2+/-11.3 cmH2O vs 6.2+/-2.0 cmH2O, P OR =70%, n=4 vs low purity <70%, n=13) in the purified group, showed significant hemodynamic stability in the high purity group, but no significant difference in the islet recovery rate between the low and high purity group(58.6% vs 61.7%). Glucose was controlled in 3 cases(25.0%) in the unpurified group and 7 cases(41.2%) in the purified group. Death due to portal hypertension occurred in 2 cases(16.7%) in unpurified group and 2 cases(11.7%) in the purified group. Interestingly, in the highly purified group, all the animals were alive with normoglycemia during the follow up period. We conclude that purified pancreas islet cell transplantation, especially in a highly purified group, has distinct hemodynamic advantages compared with unpurified islet transplantation following intraportal islet injection. However further research to develop the methods that will minimize the loss of islet yields during purification and enhance the purity is neccessary to achieve a successful islet transplantation with a long-term good result.
Subject(s)
Animals , Body Weight , Collagenases , Follow-Up Studies , Glucose , Heart Rate , Hemodynamics , Hypertension, Portal , Islets of Langerhans Transplantation , Islets of Langerhans , Pancreas , Portal Pressure , TransplantsABSTRACT
Ten cases of type I diabetes mellitus were treated with intracerebral pancreas islet transplantation. In 7 cases insulin has been totally stopped for 2 to 13 months, in other 2 cases the dosages of insulin had a decrease of 37% and 64% than that before transplantation respectively, and good control was achieved in those 9 patients. Only one case had not any improvement. The results showed that it is an effective therapy for type I diabetes mellitus and indicated that the pancreas islet was survived in patient's cerebrum and secreted insulin. No evidence of immunological rejection was found. Long-term follow-up is necessary to find how long the allogenic graft can survive.