Alternative therapeutic strategies in diabetes management.

Diabetes is a heterogeneous metabolic disease characterized by elevated blood glucose levels resulting from the destruction or malfunction of pancreatic ß cells, insulin resistance in peripheral tissues, or both, and results in a non-sufficient production of insulin. To adjust blood glucose levels, diabetic patients need exogenous insulin administration together with medical nutrition therapy and physical activity. With the aim of improving insulin availability in diabetic patients as well as ameliorating diabetes comorbidities, different strategies have been investigated. The first approaches included enhancing endogenous ß cell activity or transplanting new islets. The protocol for this kind of intervention has recently been optimized, leading to standardized procedures. It is indicated for diabetic patients with severe hypoglycemia, complicated by impaired hypoglycemia awareness or exacerbated glycemic lability. Transplantation has been associated with improvement in all comorbidities associated with diabetes, quality of life, and survival. However, different trials are ongoing to further improve the beneficial effects of transplantation. Furthermore, to overcome some limitations associated with the availability of islets/pancreas, alternative therapeutic strategies are under evaluation, such as the use of mesenchymal stem cells (MSCs) or induced pluripotent stem cells for transplantation. The cotransplantation of MSCs with islets has been successful, thus providing protection against proinflammatory cytokines and hypoxia through different mechanisms, including exosome release. The use of induced pluripotent stem cells is recent and requires further investigation. The advantages of MSC implantation have also included the improvement of diabetes-related comorbidities, such as wound healing. Despite the number of advantages of the direct injection of MSCs, new strategies involving biomaterials and scaffolds have been developed to improve the efficacy of mesenchymal cell delivery with promising results. In conclusion, this paper offered an overview of new alternative strategies for diabetes management while highlighting some limitations that will need to be overcome by future approaches.

Machanism of methyleugenoc in protecting islet cells from hypoxia/reoxygenation injury / 中华器官移植杂志

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.

[68Ga]Ga-NOTA-MAL-Cys39-exendin-4, a potential GLP-1R targeted PET tracer for the detection of insulinoma.

Glucagon-like peptide-1 receptor (GLP-1R) is a kind of G protein coupled receptor which regulates the insulin secretion and serves as potential target in the diagnosis of functional pancreas neuroendocrine tumor. The aim of this study was to evaluate the feasibility of GLP-1R targeted tracer [68Ga]Ga-NOTA-MAL-Cys39-exendin-4 in the detection of insulinoma. METHODS: NOTA-MAL-Cys39-exendin-4 was synthesized and then radiolabeled with gallium-68 in iQS® Ga-68 Fluidic Labeling Module. The in vitro binding affinity and cell uptake studies were evaluated in INS-1 cells. The in vivo micro-PET/CT imaging and biodistribution studies were performed on INS-1 xenograft tumor models. RESULTS: [68Ga]Ga-NOTA-MAL-Cys39-exendin-4 can be efficiently radiolabelled with a yield of about 85% (non-decay corrected) and radiochemical purity of >95% with a favorable stability. The molar activity was at least 145.5 GBq/µmol. The affinity (IC50) for [68Ga]Ga-NOTA-MAL-Cys39-exendin-4 was 12.99 ±â€¯0.81 nM. Micro-PET/CT images showed intense tumor uptake with good contrast to background. Biodistribution study showed the predominant uptake was in the kidney, followed by pancreas, and the liver and spleen just showed mild uptake in the blood-pool phase with rapid clearance. At 1 h post- injection, the tumor to blood, muscle and pancreas ratios were 30.64, 40.21 and 6.46, respectively. Blocking studies showed significantly decreased tumor uptake, which further confirmed binding affinity of [68Ga]Ga-NOTA-MAL-Cys39-exendin-4 to GLP-1R. CONCLUSION: [68Ga]Ga-NOTA-MAL-Cys39-exendin-4 was easily synthesized with high yield, favorable biodistribution and high affinity to islet tumor cell, making the tracer may have great potential in the detection of GLP-1R positive tumor such as an insulinoma.

Clinical Efficacy of Modified Bingtitang in Treatment of Type 2 Diabetes Mellitus and Effect on Pancreas Islet Function / 中国实验方剂学杂志

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.

Investigating the Molecular Mechanism of Aqueous Extract of Cyclocarya paliurus on Ameliorating Diabetes by Transcriptome Profiling.

Diabetes is generally regarded as a metabolic disorder disease caused by various reasons, including pancreas islet injury and lipid metabolism disorders. The aqueous extract of Cyclocarya paliurus leaves (CPAE) was reported to be anti-diabetic. However, the possible molecular mechanisms have not been investigated. To elucidate the anti-diabetic effects of CPAE and the underlying potential mechanisms, we performed transcriptome profiling (RNA-Seq and miRNA-Seq) on the pancreas and liver from non-diabetic, diabetic and diabetic-CPAE rats. Our results demonstrated the CPAE could reduce excessive oxidative stress and inflammation in the pancreas, and maintain the balance of glucose and lipid metabolism in the liver. Transcriptome profiling and regulatory network analysis indicated that CPAE may ameliorate diabetes through improving ß-cell survival and strengthening insulin secretion in the pancreas. Meanwhile, CPAE could improve impaired lipid metabolism and reduce excessive oxidative damage in the liver probably through miR-200/375-Aldh1b1/Hps5-Hes1 co-regulatory network. Taken together, our biochemical experiments combined with transcriptome profiling showed that the effects of CPAE on anti-diabetes may work through protecting pancreatic ß-cell, improving dyslipidaemia and lipid metabolism disorders.

Chronic chlorpyrifos exposure elicits diet-specific effects on metabolism and the gut microbiome in rats.

Chlorpyrifos is a commonly-used pesticide which was reported to interfere with hormone signaling and metabolism, however, little is known about its effect on gut microbiota. In this study, adult male rats fed a normal (NF) or high fat (HF) diet were exposed to 0.3 or 3.0 mg chlorpyrifos/kg bodyweight/day or vehicle alone for 9 weeks. Effects on bodyweight, serum levels of glucose, lipid, cytokines, and gut microbiome community structure were measured. The effects of chlorpyrifos on metabolism were dose- and diet-dependent, with NF-fed rats administered the low dose showing the largest metabolic changes. NF-fed rats exposed to chlorpyrifos exhibited a pro-obesity phenotype compared with their controls, whereas there was no difference in pro-obesity phenotype between HF-fed groups. Chlorpyrifos exposure significantly reduced serum insulin, C-peptide, and amylin concentrations in NF- and HF-fed rats, leaving serum glucose and lipid profiles unaffected. Chlorpyrifos exposure also significantly altered gut microbiota composition, including the abundance of opportunistic pathogens, short chain fatty acid-producing bacteria and other bacteria previously associated with obese and diabetic phenotypes. The abundance of bacteria associated with neurotoxicity and islet injury was also significantly increased by chlorpyrifos. Our results suggest risk assessments for chlorpyrifos exposure should consider other effects in addition to neurotoxicity.

Islet ß cell: An endocrine cell secreting miRNAs.

The pancreas is an important endocrine organ. Pancreatic beta (ß) cells secrete insulin to regulate the metabolism of glucose and maintain the stability of blood glucose. MicroRNAs (miRNAs), small (20-25 nt) non-coding RNA molecules, function in target gene silencing through post-transcriptional patterns, and multiple miRNAs regulate insulin secretion, insulin signaling pathways in pancreatic ß cells and islet activity. In recent years, it has been found that many types of cells can secrete regulatory miRNA, but whether islet cells can secrete miRNA has not been clarified yet. In this study, we detected miRNA expressions in cell culture medium of primary mouse islet cells and islet cell line MIN6. And we found that islet cells can selectively and actively secrete miRNAs, mainly through the way of exosome package, and that miRNA secretion profiling patterns vary according to different insulin secretion stimulating conditions (high Glucose, high Kcl, high Arginine and high Free fat acid (FFA)). Additionally, we found that these miRNAs secreted by islet cells can be transported and have gene-regulating functions on recipient tissue cells, such as liver and muscles. In conclusion, we find another secretory function of the islet ß cells: not only insulin, but also miRNAs.

ATP synthase ß-subunit abnormality in pancreas islets of rats with polycystic ovary syndrome and type 2 diabetes mellitus.

This study investigated the abnormal expression of ATP synthase ß-subunit (ATPsyn-ß) 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-ß 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-ß. 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-ß 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-ß in the pancreas islets transfected with lenti-ATP5b. These results indicated that for PCOS, the ATPsyn-ß might be one of the key factors for the attack of T2DM.

Real architecture For 3D Tissue (RAFT™) culture system improves viability and maintains insulin and glucagon production of mouse pancreatic islet cells.

There is an unmet medical need for the improvement of pancreatic islet maintenance in culture. Due to restricted donor availability it is essential to ameliorate islet viability and graft engraftment. The aim of this study was to compare the standard tissue culture techniques with the advanced Real Architecture For 3D Tissue (RAFT™) culture system in terms of viability and hormone production. Here, we first report that islets embedded in RAFT™ collagen type I advanced tissue culture system maintain their tissue integrity better than in monolayer and suspension cultures. The Calcein violet assay and Annexin V/propidium-iodide staining show higher cell viability in the RAFT™ culture system. Quantitative real-time PCR data showed that RAFT™ increases insulin expression after 18 days in culture compared to traditional methods. Enhanced insulin and glucagon production was further verified by immunofluorescent staining in a time-course manner. These results indicate that RAFT™ tissue culture platform can be a promising tool to maintain pancreatic islet spheroid integrity and culture islets for downstream high throughput pharmacological studies ex vivo.

ATP Synthase β-subunit Abnormality in Pancreas Islets of Rats with Polycystic Ovary Syndrome and Type 2 Diabetes Mellitus / 华中科技大学学报（医学）（英德文版）

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.

[Exploration on the treatment of xiaoke in terms of the conception vessel].

Diabetes is in the category of xiaoke in TCM, which is mainly discussed in light of yin deficiency. The conception vessel is the sea of yin meridians, acting on regulating the accumulation and irrigation of qi and blood of twelve meridians and collaterals. The physiological function of the conception vessel is closely related to the pathogenesis of xiaoke, its running course is highly coincident with the location of xiaoke and the symptoms of xiaoke are relevant with the indications of the conception vessel. Hence, harmonizing qi and blood of the conception vessel may be an effective approach to the prevention and treatment of xiaoke.

Effects on pancreas islet function in patients undergoing laparoscopic myomectomy during sevoflurane and propofol anesthesia / 临床麻醉学杂志

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.

Exploration on the treatment ofin terms of the conception vessel / 中国针灸

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.

Different effects of statins on induction of diabetes mellitus: an experimental study.

BACKGROUND: To determine the effect of different statins on the induction of diabetes mellitus. MATERIALS AND METHODS: Four statins (atorvastatin, pravastatin, rosuvastatin, and pitavastatin) were used. Cytotoxicity, insulin secretion, glucose-stimulated insulin secretion, and G0/G1 phase cell cycle arrest were investigated in human pancreas islet ß cells, and glucose uptake and signaling were studied in human skeletal muscle cells (HSkMCs). RESULTS: Human pancreas islet ß cells treated with 100 nM atorvastatin, pravastatin, rosuvastatin, and pitavastatin had reduced cell viability (32.12%, 41.09%, 33.96%, and 29.19%, respectively) compared to controls. Such cytotoxic effect was significantly attenuated by decreasing the dose to 10 and 1 nM, ranged from 1.46% to 17.28%. Cells treated with 100 nM atorvastatin, pravastatin, rosuvastatin, and pitavastatin had a reduction in the rate of insulin secretion rate by 34.07%, 30.06%, 26.78%, and 19.22%, respectively. The inhibitory effect was slightly attenuated by decreasing the dose to 10 and 1 nM, ranging from 10.84% to 29.60%. Insulin secretion stimulated by a high concentration of glucose (28 mmol/L) was significantly higher than a physiologic concentration of glucose (5.6 mmol/L) in all treatment groups. The glucose uptake rates at a concentration of 100 nM were as follows: atorvastatin (58.76%) < pravastatin (60.21%) < rosuvastatin (72.54%) < pitavastatin (89.96%). We also found that atorvastatin and pravastatin decreased glucose transporter (GLUT)-2 expression and induced p-p38 MAPK levels in human pancreas islet ß cells. Atorvastatin, pravastatin, and rosuvastatin inhibited GLUT-4, p-AKT, p-GSK-3ß, and p-p38 MAPK levels in HSkMCs. CONCLUSION: Statins similar but different degree of effects on pancreas islet ß cells damage and induce insulin resistance in HSkMC.

Effect of gastric bypass surgery on fasting blood glucose and pancreatic islet cell in type 2 diabetic rats / 中华内分泌外科杂志

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.

Extracellular matrix improves islet cell survival by α3-integrin regulation / 中华肝胆外科杂志

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.

Effects of carbohydrate-electrolyte solution on serum glucose, pancreas islet function, and safety in elderly patients after abdominal operation / 中华临床营养杂志

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.

Clinical Islet Transplantation: Where Do We Stand on? / 대한이식학회지

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.

Pancreas Islet Cell Transplantation: Present and Future / 한양의대학술지

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.

Comparative Study on Biologic and Immunologic Characteristics of the Pancreas Islet Cell between 24degrees C and 37degrees C Culture in the Rat / 대한이식학회지

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.