The insulin secretion of a minced neonatal rat pancreas cultured in a pancreatic chamber, in response to various insulin secretagogues.
YOSHIMASA ARAKIKuninori YoshiokaYasunori InoueYoshio NakamuraNaoto NakamuraKoji NakanoToshihide YoshidaMotoharu Kondo
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Abstract:
The minced pancreas of the neonatal rat was cultured for 35 days in a pancreatic chamber which was constructed of a plastic tube and an ultrafiltration membrane. Insulin and amylase secreted from this pancreatic chamber into the culture medium were measured. During the experiment, the concentration of glucose in the culture medium was changed between 5.5 and 16.5 mM at 2-3 day intervals in order to determine the insulin secretory response of the pancreatic tissue. Insulin secretion was markedly increased in response to 16.5 mM glucose. The ratio of insulin secretion to amylase secretion in the culture medium increased with the advance of culture days although secretions of both insulin and amylase decreased individually. On the 7th culture day, short term incubations were performed to test with various insulin secretagogues; obvious insulin release into the incubation medium was observed. These results show that the pancreatic chamber also in vitro secretes insulin rapidly and significantly in response to various stimuli; that by longer culture of a neonatal rat pancreas in this device, insulin secretory cells without exocrine tissue would be obtained without using digestive enzymes; that application of a pancreatic chamber for a pancreatic transplantation may be feasible.Keywords:
Pancreas transplantation
Insulin oscillation
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Objective Length of hospital stay is a sensitive indicator of short-term prognosis. In this retrospective study, we investigated how pancreas preservation time affects length of hospital stay after pancreas transplantation. Methods Patients receiving pancreas transplantation (1998.7–2018.6) were identified from the Scientific Registry of Transplant Recipients database and grouped according to pancreas preservation time. We analyzed the relationship of pancreas preservation time with graft and patient survival and prolonged length of stay (PLOS; i.e., hospital stay ≥20 days). Results We included 18,099 pancreas transplants in the survival analysis. Pancreas preservation time >20 hours had a significantly higher risk of graft failure than 8 to 12 hours. Pancreas preservation time was not significantly associated with patient survival. We included 17,567 pancreas transplants in the analysis for PLOS. Compared with 8 to 12 hours, pancreas preservation time >12 hours had a significantly higher PLOS risk, which increased with increased pancreas preservation time. In simultaneous pancreas–kidney transplantation, we also found that pancreas preservation time was positively associated with PLOS risk with pancreas preservation time >12 hours. Conclusion Pancreas preservation time is a sensitive predictor of PLOS. Transplant centers should minimize pancreas preservation time to optimize patient outcomes.
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Introduction: The early diagnosis of pancreas allograft rejection after single pancreas or simultaneous pancreas/kidney transplantation is essential for adequate anti-rejection therapy and long term graft survival. In simultaneous pancreas/kidney transplantation it has been shown that the absence of histological rejection in kidney biopsies is not always indicative for absence of rejection in the pancreas. Due to the potential spectrum of complications, pancreas allograft biopsies are performed reluctantly. Here, we report on our results on cause-biopsies of the pancreas and kidney allografts. Methods: All allografts were monitored during follow up after transplantation by contrast-enhanced ultrasound using a Acuson Sequoia (Siemens Medical Solutions) and 1ml of SonoVue® (BRACCO). The indication to biopsy was given if organ function deteriorated (elevated fasting blood-glucose and/or increased pancreas enzymes or impaired kidney function) and no other underlying cause was detected. Causebiospies of the pancreas graft were performed under ultrasound- or computertomography (CT) guidance. The kidney graft was biopsized exclusively by ultrasound due to its easy accessibility. Histopathologic evaluation was performed at an external reference center. Results: A total of 13 pancreas transplantations have been performed at our center since 2008, thereof 1 patient with pancreoprive diabetes and 12 patients with type 1 diabetes and end-stage renal disease (10 simultaneous pancreas/kidney, 1 pancreas after kidney and 1 pancreas re-transplantation). During follow up 12 cause-biopsies of pancreasallografts were indicated in 7 patients due to elevated fasting blood glucose or increased pancreas enzymes. In 5 patients biopsies were performed under ultrasound guidance, in 2 patients via CT-monitoring. Two biopsies resulted in insufficient material and had to be repeated. By histopathological examination, 5 rejection episodes of different degree (BANFF III, IIa, II, I) were found in 4 patients and treatment with Predisone- or Thymoglobulin pulse-therapy was initiated. An exclusive kidney-allograft rejection was diagnosed in 1 patient that was previously treated for pancreas-allograft rejection. No complications occured, neither after ultrasound- nor computertomography guidance occurred. Conclusion: Cause-biospies of pancreas-allografts can be performed safely under contrast-enhanced ultrasound or computertomography guidance. Especially contrast-enhanced ultrasound appears to be an excellent method for pancreas allograft surveillance and biopsy in experienced hands. Even though the cohort is relatively small, our results suggest that a simultaneous rejection of the pancreas and kidney allograft is a rare event.
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There had been few if any study for second pancreas transplant outcome and consequences in patients with simultaneous kidney pancreas transplant after failure of the first pancreas allograft. The aim of this study was to compare the patient and graft survival and clinical outcomes and complication of the second pancreas transplant in patients with simultaneous kidney pancreas, compared with pancreas after kidney transplantation in patients with no history of previous failed pancreas graft failure. Two groups of patients, patients with simultaneous kidney pancreas transplantation with pancreas graft failure (11 patients) and kidney transplant patients with no history of previous pancreas transplant having first pancreas transplantation (6 patients) were statistically compared. Immediate and short time difference in survival rate between group 1 and group 2 was 63% and 33%, respectively. The difference was attributable to more vascular thrombosis ending in graft loss in group 1, but this dose not achieve a statistical significance ( P = 0.7); although long term survival rate difference was more evident and significant ( P = 0.002). The only other statistically difference found between two groups was the donor's age with a P value of 0.02, in favor of the patients in group 2, who have received grafts from younger donors. The long term pancreas graft survival rate in patients with the history of previous pancreas transplantation in the setting of SKP is worse than pancreas graft survival in previously kidney transplanted patients, receiving their first pancreas in pancreas after kidney setting.
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Pancreas transplantation
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Pancreas transplantation provides the only proven method to restore long-term normoglycemia in patients with insulin-dependent diabetes mellitus. Although many studies describe the most important risk factors for short-term survival of a pancreas transplant, more information about factors that distinguish short-term from long-term graft function is needed.Analysis of 21 328 pancreas transplants from the International Pancreas Transplant Registry, performed from 1984 to 2009 (minimum 5-year follow-up), shows a significant improvement in long-term patient survival and pancreas graft function. Total 5-and 10-year pancreas graft function rates are 73 and 56%, respectively, for simultaneous pancreas-kidney transplants; 64 and 38%, respectively, for pancreas after kidney; and 53 and 36%, respectively, for pancreas transplants alone. The most influential period is the first year posttransplant. Recipients who reach this time point with a functioning graft have a much higher probability for excellent long-term graft function. Important factors influencing long-term function were features that described the quality of the deceased donor. Pancreas transplants in younger, high panel reactive antibody, or African-American recipients also showed an increased risk of early graft failure. Anti-T-cell induction therapy had a significant impact on long-term survival in solitary transplants.With careful recipient and donor selection and close follow-up in the first year posttransplant, not only good short-term but also long-term pancreas graft function and, therefore, durable metabolic control can be achieved for the diabetic patient.
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In the eight years since the initiation of pancreas transplantation at our center, 36 patients have received either segmental or whole pancreas grafts. Seventeen patients had segmental pancreas allografts, with eight of these receiving simultaneous kidney allografts from the same donor. Nineteen patients received whole pancreas and kidney allografts. Thirty five of the pancreases were preserved using hypothermic storage for up to 43 hours and 45 minutes, using either albumin-augmented crystalloid or hyperosmolar colloid preservation solution. The one-year actuarial graft survival was 12 per cent for segmental pancreas transplants and 42 per cent for whole pancreas grafts. The use of cyclosporine after whole pancreas transplantation as well as improved surgical techniques for exocrine drainage contributed to the improvement in graft survival in the whole pancreas graft group.
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