Rapamycin induces autophagy in islets: relevance in islet transplantation.

Abstract:

:Islet transplantation can provide insulin independence in patients with type 1 diabetes mellitus. However, islet allograft recipients exhibit a gradual decline in insulin independence, and only 10% do not require insulin at 5 years. This decline may reflect drug toxicity to islet beta cells. Rapamycin, a central immunosuppressant in islet transplantation, is a mammalian target of rampamycin inhibitor that induces autophagy. The relative contributions of autophagy in transplanted islets are poorly understood. Therefore, in the present study we sought to evaluate the effects of rapamycin on islet beta cells. Rapamycin treatment of islets resulted in accumulation of membrane-bound light chain 3 (LC3-II) protein, an early marker of autophagy. In addition, rapamycin treatment of isolated islets elicited not only reduction of viability but also downregulation of in vitro potency. To further examine the occurrence of autophagy in rapamycin-treated islets, we used GFP (green fluorescent protein)-LC3 transgenic mice that express a fluorescent autophagosome marker. The GFP-LC3 signals were markedly increased in rapamycin treated islets compared with control islets. In addition, to show improvement by blockade of autophagic signaling, islets were treated with rapamycin in the presence of 3-methyladenine, which inhibits autophagy. Thereafter, both islet viability and islet potency were dramatically improved. The number of GFP-LC3 dots clearly increased after 3-MA treatment. Thus, rapamycin treatment of islets induces autophagy in vitro. This phenomenon may contribute to the progressive graft dysfunction of transplanted islets. Therapeutically targeting this novel signaling may yield significant benefits for long-term islet survival.

journal_name

Transplant Proc

authors

Tanemura M,Saga A,Kawamoto K,Machida T,Deguchi T,Nishida T,Sawa Y,Doki Y,Mori M,Ito T

doi

10.1016/j.transproceed.2008.10.032

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

334-8

issue

1

eissn

0041-1345

issn

1873-2623

pii

S0041-1345(08)01457-7

journal_volume

41

pub_type

杂志文章
  • Functional and histological comparison of rat liver preserved in University of Wisconsin solution compared with tissue preserved in a novel solution.

    abstract::An isolated perfused rat liver model was used to investigate biochemical and histologic changes during 2 hours of reperfusion after 24 hours of cold storage to compare Leeds solution (LS) with University of Wisconsin solution (UW). Compared with livers stored in UW, those perfused with LS showed significantly higher b...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2010.06.029

    authors: Corps CL,Ahmed I,McKenzie S,Shires M,Potts DJ,Lodge JP

    更新日期:2010-11-01 00:00:00

  • New immunosuppressive therapies and surgical complications after renal transplantation.

    abstract:BACKGROUND:To analyze the association between the principal immunosuppressive drugs (mycophenolate mofetil, calcineurin inhibitors and mammalian target of rapamycin [mTOR] inhibitors) used in the routine management of kidney transplant patients and the development of postoperative surgical complications. MATERIALS AND...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2012.01.112

    authors: Barba J,Rosell D,Rincon A,Robles JE,Zudaire J,Berian JM,Pascual I,Errasti P

    更新日期:2012-06-01 00:00:00

  • Factors related to post-liver transplantation acute renal failure.

    abstract::Acute renal failure (ARF) after liver transplantation (OLT) is a common complication with severe impact on early and late prognosis of recipients. Factors predicting its incidence have not been fully identified due to the lack of a universal standard as well as the variance of data between transplant centers. To ident...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2006.08.156

    authors: Wei Y,Zhang L,Lin H,Li J,Li B,Yan L,Wen T,Zeng Y,Lu S

    更新日期:2006-11-01 00:00:00

  • How long should we follow the post-transplantation patient after graft loss? A case report of renal cancer in the grafted kidney that occurred 16 years after graft loss.

    abstract:BACKGROUND:Renal cancers commonly occur in the native kidneys of renal transplant recipients, whereas renal cancer in the grafted kidney has been reported occasionally. Renal cancer in the grafted kidney occurred 16 years after graft loss in this case, which would be a more rare case. CASE REPORT:A 60-year-old man who...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2013.11.017

    authors: Akioka K,Masuda K,Harada S,Nakao T,Nakamura T,Okugawa K,Nakano K,Osaka Y,Tsuchiya K,Sako H

    更新日期:2014-01-01 00:00:00

  • The impact of experience of a transplantation center on the outcomes of orthotopic liver transplantation.

    abstract::The so-called learning factor has been disregarded for many years in analyzing the causes of surgical complications and post-operative mortality; it is also the case for OLT. In our center until April 2003, 209 OLT were performed in 196 patients. We evaluated the impact of experience of the transplantation team on the...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/s0041-1345(03)00834-0

    authors: Krawczyk M,Grzelak I,Zieniewicz K,Nyckowski P,Pawlak J,Michałowicz B,Patkowski W,Alsharabi A,Wróblewski T,Paluszkiewicz R,Małkowski P,Hevelke P,Pszenny C,Remiszewski P,Skwarek A,Smoter P,Grodzicki M,Kornasiewicz O,Kor

    更新日期:2003-09-01 00:00:00

  • Experience with cyclosporine in the Canary Islands.

    abstract::Cyclosporine (CsA) is currently the basis of most immunosuppressive protocols after solid organ transplantation. The introduction of Neoral, a new microemulsion formulation of CsA, and more recently a range of adjunctive immunosuppressants have further enhanced short-term efficacy and tolerability of CsA-based immunos...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章,评审

    doi:10.1016/j.transproceed.2003.12.030

    authors: Hernández D

    更新日期:2004-03-01 00:00:00

  • Experience using extended criteria donors in first 100 cases of deceased donor liver transplantation in Japan.

    abstract::Because of the serious organ shortage in Japan, the use of extended criteria (EC) donors is inevitable to increase the number of deceased donors. However, the influence of this practice on recipient outcomes has not been clarified yet. We analyzed donor and recipient factors to determine whether those factors, especia...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2012.01.010

    authors: Furukawa H,Taniguchi M,Fujiyoshi M,Oota M,Japanese Study Group of Liver Transplantation.

    更新日期:2012-03-01 00:00:00

  • Does multiorgan versus kidney-only cadaveric organ procurement affect graft outcomes?

    abstract:INTRODUCTION:The majority of kidney grafts in most European countries still come from deceased donors who provide other organs. We analyzed whether multiorgan procurement portends a worse functional outcome compared with kidney-only harvesting. METHODS:We performed a retrospective analysis of 1043 consecutive brain-de...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2013.02.026

    authors: Castelo D,Campos L,Moreira P,Furriel F,Parada B,Nunes P,Figueiredo A,Mota A

    更新日期:2013-04-01 00:00:00

  • Transplant Friends: an interactive education program for patients awaiting kidney transplantation.

    abstract:BACKGROUND:Organ transplantation is the preferred treatment for end-stage renal disease. Renal transplant recipients are surviving longer with a better quality of life. Although many hospitals have transplant education programs in place, transplant patients indicate that there is a need for additional information. Tran...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2003.08.010

    authors: Sharkey C,Gourishankar S

    更新日期:2003-11-01 00:00:00

  • Delayed renal function and long-term cadaver renal allograft survival.

    abstract::This study indicates that (1) ATN adversely affects long-term allograft survival but not patient survival, (2) in patients with delayed function the duration of ATN does not influence allograft survival, (3) ATN kidneys with good recovery (SCR less than 3.0) do as well as immediate-function kidneys, (4) poor recovery ...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:

    authors: Anderson CB,Sicard GA,Etheredge EE

    更新日期:1979-03-01 00:00:00

  • Use of intraperitoneal ePTFE Gore dual-mesh plus in a giant incisional hernia after kidney transplantation: a case report.

    abstract::We evaluated the incidence of and predisposing factors for an incisional hernia after kidney transplantation. Numerous techniques have been used to repair postoperative fascial dehiscences or simple incisional hernias, but no clear treatment exists for giant hernias. Our aim was to obtain (1) a safe procedure to repai...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2009.02.060

    authors: Lo Monte AI,Damiano G,Maione C,Gioviale MC,Lombardo C,Buscemi G,Romano M

    更新日期:2009-05-01 00:00:00

  • Neonatal pig pancreatic duct-derived insulin-producing cells: preliminary in vitro studies.

    abstract::Neonatal pig pancreata could represent an ideal tissue resource for donor islets for transplantation trials. Because functional islet beta-cells could derive from precursors situated in the ductal system, and neonatal animals are better suitable than adults for recovering such elements, we have examined whether isolat...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2004.03.074

    authors: Basta G,Racanicchi L,Mancuso F,Guido L,Macchiarulo G,Luca G,Calabrese G,Brunetti P,Calafiore R

    更新日期:2004-04-01 00:00:00

  • An audit of a steriod withdrawal regimen in cardiac transplantation patients.

    abstract:BACKGROUND:Heart transplantation is optimal treatment for many patients with end-stage heart failure. Current data report 1-year graft survival rates of 85% after transplantation. The success of transplantation in large part is attributable to immunosuppression, including steroids, one of the mainstay agents. Despite i...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2011.01.050

    authors: Nawaz MA,Curry P,Patni R,Punjabi P,Murday A

    更新日期:2011-03-01 00:00:00

  • Relationship between chronic inflammation and cardiovascular risk factors in children on maintenance hemodialysis.

    abstract::Cardiovascular disease is one of the most important causes of morbidity and mortality in children with end-stage renal failure. Chronic inflammation and malnutrition have been suggested to be risk factors for cardiovascular disease. However, to date, biomarkers of inflammation have not been well studied in children. T...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2005.07.058

    authors: Cengiz N,Baskin E,Agras PI,Sezgin N,Saatci U

    更新日期:2005-09-01 00:00:00

  • Organ Donation and Transplantation From Donors With Systemic Infection: A Single-Center Experience.

    abstract:OBJECTIVES:Donors with bacteremia and sepsis are often considered to be controversial for organ retrieval due to potential transmission of an infectious agent to the recipient. Herein we report our initial experience of organ donation and transplantation results from donors with systemic infection. MATERIALS AND METHO...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2016.02.092

    authors: Yuan X,Chen C,Zhou J,Han M,Wang X,Wang C,He X

    更新日期:2016-09-01 00:00:00

  • Transforming growth factor-beta signaling is enhanced following mitomycin-C treatment of islet xenograft.

    abstract::Mitomycin-C (MMC) is categorized as an agent that causes genotoxic stress by triggering various intracellular signaling pathways. We have previously shown that MMC pretreatment of highly immunogenic crude islets leads to significant prolongation of graft survival in a rat-to-mouse model. In the present study, we exami...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2004.04.029

    authors: Ise K,Sato Y,Matsuyama S,Gunji T,Ishii S,Yamashita M,Kanazawa Y,Gotoh M

    更新日期:2004-05-01 00:00:00

  • It takes time after bilateral nephrectomy for better control of resistant hypertension in renal transplant patients.

    abstract:UNLABELLED:Severe resistant hypertension in end-stage renal disease patients has traditionally been an indication for bilateral nephrectomy (BN) before kidney transplantation. Nevertheless the influence of BN on successful control of hypertension has not been well documented. We sought to clarify the effect of BN on bl...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2010.04.014

    authors: Gawish AE,Donia F,Fathi T,Al-Mousawi M,Samhan M

    更新日期:2010-06-01 00:00:00

  • Early postoperative spectral Doppler parameters of renal transplants: the effect of donor and recipient factors.

    abstract:BACKGROUND:The objective of this study was to explore the donor and recipient factors related to the spectral Doppler parameters of the transplant kidney in the early posttransplantation period. METHODS:This retrospective study included 76 patients who underwent renal transplantation assessed using Doppler ultrasonogr...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2011.12.069

    authors: Wang HK,Chiou SY,Lai YC,Cheng HY,Lin NC,Loong CC,Chiou HJ,Chou YH,Chang CY

    更新日期:2012-01-01 00:00:00

  • Multivisceral transplantation for the treatment of intra-abdominal tumors.

    abstract:BACKGROUND:Some intra-abdominal or retroperitoneal tumors such as low-grade slow-growing malignancies may seem unresectable due to major vessel encasement or presence of intra-abdominal dissemination, but the slow growth rate and to some extent long life expectancy of the patients urge us to find some strategies to cur...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2013.09.002

    authors: Nikeghbalian S,Aliakbarian M,Shamsaeefar A,Kazemi K,Bahreini A,Malekhosseini SA

    更新日期:2013-01-01 00:00:00

  • Cost of renal transplant maintenance immunosuppression: effect of control of vascular risk factors.

    abstract::In 3 renal transplant cohorts treated in Spain in 1990, 1994, and 1998 (total number, 3279), we studied the frequency of certain cardiovascular risk factors. Their effect on the cost of drugs was assessed from the data from 1 center; the mean cost of antihypertensive agents per patient-year was 349 euros, and of lipid...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2005.02.011

    authors: Gentil MA,López M,González-Roncero F,Cantarell C,Marco J

    更新日期:2005-04-01 00:00:00

  • Results of retransplantation for primary nonfunction in a single center.

    abstract:INTRODUCTION:Early graft dysfunction has a negative impact on allograft and patient survivals, evolving to retransplantation or death in the majority of cases. The outcome of a second liver transplant is usually worse than the first procedure. Considering the increasing number of recipients on the waiting list, and the...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2010.12.003

    authors: Coelho MP,Afonso RC,Hidalgo R,Felga G,Almeida MD,Della-Guardia B,Rezende MB,Meira-Filho SP,Ferraz-Neto BH

    更新日期:2011-01-01 00:00:00

  • Experience with Alemtuzumab (Campath-1H) as induction agent in renal transplantation followed by steroid-free immunosuppression.

    abstract:BACKGROUND:The purpose of this study was to describe the initial experience with alemtuzumab as induction followed by steroid-free immunosuppression in kidney transplantation. METHODS:One hundred patients who received renal transplants from living and deceased donors were followed for a median period of 12 months (ran...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2008.02.026

    authors: Baez Y,Giron F,Niño-Murcia A,Rodríguez J,Salcedo S

    更新日期:2008-04-01 00:00:00

  • A new kidney allocation policy in Chile: computer-based simulations.

    abstract:INTRODUCTION:Kidney allocation should reach a balance between equity and efficiency. In Chile kidneys are allocated based on ABO matching, first to medical priorities and then according to a point scheme considering human leukocyte antigen (HLA) match (60%), waiting list time (20%), and panel-reactive antibodies (PRA; ...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2013.01.012

    authors: Domínguez J,Harrison R,Atal R,Muñoz F

    更新日期:2013-05-01 00:00:00

  • Bacterial Pathogens Isolated in Liver Transplant Recipients With Surgical Site Infection and Antibiotic Treatment.

    abstract:OBJECTIVE:Surgical site infection (SSI) is the most common infection after liver transplantation in our hospital. In this study, the effect of microorganisms isolated in liver transplant recipients' (LTRs') culture with SSI on antibiotic treatment has been investigated. METHOD:Between January 2003 and December 2013, m...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2015.04.047

    authors: Avkan-Oguz V,Unek T,Firuzan E,Ozbılgın M,Egelı T,Bacakoglu A,Gulay Z,Astarcıoglu I

    更新日期:2015-06-01 00:00:00

  • Static Cold Storage vs Ex Vivo Machine Perfusion: Results From a Comparative Study on Renal Transplant Outcome in a Controlled Donation After Circulatory Death Program.

    abstract:INTRODUCTION:We aimed to evaluate if ex vivo machine perfusion could minimize the negative impact of cold ischemia on those renal grafts obtained from controlled donation after circulatory death (cDCD). MATERIAL AND METHODS:Prospective observational paired study of kidney transplants from cDCD performed in our center....

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2018.12.010

    authors: Arlaban M,Barreda P,Ballesteros MA,Rodrigo E,Suberviola B,Valero R,Miñambres E,Ruiz-San Millán JC

    更新日期:2019-03-01 00:00:00

  • Contamination of the Preservation Solution in Solid Organ Transplantation.

    abstract:INTRODUCTION:Preservation solutions (PS), in which grafts for patients undergoing liver transplantation are stored, represent a medium suitable for microorganism growth and a potential source for transmission of pathogenic germs to the transplant recipients. The aim of the present study was to review the relevant liter...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章,评审

    doi:10.1016/j.transproceed.2019.01.070

    authors: Sotiropoulos GC,Kostakis ID,Prodromidou A,Garoufalia Z,Stamopoulos P,Machairas N

    更新日期:2019-03-01 00:00:00

  • Cryopreservation of immobilized rat hepatocytes for the development of a bioartificial liver system.

    abstract::Liver transplantation, the only effective treatment for end-stage disease, is limited by donor availability. Cell transplantation offers the possibility to restore liver mass and function. Cryopreserved primary hepatocytes that can be thawed as needed might address this problem. Hepatocytes were harvested from a male ...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2012.03.050

    authors: Lee JH,Park JH,Park HJ,General T,Cho MG,Lee SK

    更新日期:2012-05-01 00:00:00

  • Acute effects of a single dose of phosphodiesterase type 5 inhibitor (sildenafil) on systemic arterial blood pressure during exercise and 24-hour ambulatory blood pressure monitoring in heart transplant recipients.

    abstract:BACKGROUND:Arterial systemic hypertension (SH) can be associated with a decrease in endothelium-dependent nitric oxide (NO). Sildenafil increases cyclic guanosine monophosphate (cGMP), a mediator of NO. However, little is known about the effects of PDE5 inhibition on 24-hour ambulatory pressure (ABP) and exercise blood...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.transproceed.2007.04.029

    authors: Guimaraes GV,d'Avila VM,Pires P,Bacal F,Stolf N,Bocchi E

    更新日期:2007-12-01 00:00:00

  • Liver transplantation in pigs with small-for-size grafts: effect of portocaval shunt.

    abstract::Small-for-size livers are associated with graft dysfunction, probably due to portal hyperperfusion. Modulation of the recipient portal inflow is a new option in these cases. This article sought to analyze the effect of portocaval shunt in small-for-size liver grafts in pigs. Twelve liver transplants were performed in ...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2004.03.054

    authors: Reichert PR,Pires JS,Sallet CA,Brun MV,Vesco JD,Bonadeo NM,Missel J,Sossela R,Rodrigues R,Fracasso JI,Malheiros AV,Bajerski JC,Annes RD,Guimarães TT,Santos FC,Ben AJ,Gressler M,Wolff NM,Winkelmann G,Manzatto LB,Sa

    更新日期:2004-05-01 00:00:00

  • Prevalence of anemia in renal transplant patients: results from MOST, an observational trial.

    abstract:INTRODUCTION:Anemia is one of the most common complications of chronic renal disease. However, the incidence or prevalence of anemia in kidney transplant recipients has not been well studied. The aim of this study was to assess the prevalence of anemia in renal transplant in early and late posttransplant period and the...

    journal_title:Transplantation proceedings

    pub_type: 杂志文章

    doi:10.1016/j.transproceed.2005.10.054

    authors: Fernández Fresnedo G,Palomar R,Rodrigo E,Ruiz JC,de Francisco AL,Cotorruelo JG,Arias M

    更新日期:2005-11-01 00:00:00