Adenovirus-mediated XIAP gene transfer reverses the negative effects of immunosuppressive drugs on insulin secretion and cell viability of isolated human islets.

Abstract:

:Immunosuppressive drugs are routinely used to provide tolerance after whole pancreas and islet cell transplantations. While they are essential in inhibiting graft rejection, little is known about their effect on islet function and beta-cell viability. In this study, we report that tacrolimus, sirolimus, and mycophenolic acid, when added to cultures of freshly isolated human islets, induce a downregulation of the synthesis and secretion of insulin. These functional changes are associated with decreased islet cell viability. All three agents induce a decrease of intracellular levels of Bcl-2 and Bcl-xL, with an increased level of Smac, indicating that they are capable of promoting a downregulation of anti-apoptotic factors and an accumulation of pro-apoptotic mediators. Transduction of islet cells with the anti-apoptotic gene XIAP prevents the negative effects of these drugs on the function and viability of islets. XIAP-infected cells show a higher expression of phospho-CREB (cAMP-responsive element binding protein) and a reduced level of Smac, resulting in a significant reduction of apoptotic cells and a preservation of the glucose-dependent secretion of insulin. In conclusion, the present study demonstrates that genetically modified human islets expressing XIAP are resistant to the negative effects of immunosuppressive drugs on insulin secretion and cell viability.

journal_name

Diabetes

journal_title

Diabetes

authors

Hui H,Khoury N,Zhao X,Balkir L,D'Amico E,Bullotta A,Nguyen ED,Gambotto A,Perfetti R

doi

10.2337/diabetes.54.2.424

subject

Has Abstract

pub_date

2005-02-01 00:00:00

pages

424-33

issue

2

eissn

0012-1797

issn

1939-327X

pii

54/2/424

journal_volume

54

pub_type

杂志文章

相关文献

DIABETES文献大全
  • Regulation and function of the muscle glycogen-targeting subunit of protein phosphatase 1 (GM) in human muscle cells depends on the COOH-terminal region and glycogen content.

    abstract::G(M), the muscle-specific glycogen-targeting subunit of protein phosphatase 1 (PP1) targeted to the sarcoplasmic reticulum, was proposed to regulate recovery of glycogen in exercised muscle, whereas mutation truncation of its COOH-terminal domain is known to be associated with type 2 diabetes. Here, we demonstrate dif...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.9.2221

    authors: Lerín C,Montell E,Nolasco T,Clark C,Brady MJ,Newgard CB,Gómez-Foix AM

    更新日期:2003-09-01 00:00:00

  • Glucose transporter-1 in the hypothalamic glial cells mediates glucose sensing to regulate glucose production in vivo.

    abstract:OBJECTIVE:Circulating glucose inhibits glucose production in normal rodents and humans, but this glucose effectiveness is disrupted in diabetes due partly to sustained hyperglycemia. We hypothesize that hyperglycemia in diabetes impairs hypothalamic glucose sensing to lower glucose production, and changes of glucose tr...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-0120

    authors: Chari M,Yang CS,Lam CK,Lee K,Mighiu P,Kokorovic A,Cheung GW,Lai TY,Wang PY,Lam TK

    更新日期:2011-07-01 00:00:00

  • HLA and insulin-dependent diabetes. A protective perspective.

    abstract::This article presents a model for the HLA effect in insulin-dependent diabetes mellitus (IDDM) that is almost the mirror image of a model suggested by Nepom. In the Nepom model, the products of certain HLA alleles are associated with IDDM because they bind and present a specific peptide or peptides so as to induce an ...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diab.41.2.123

    authors: Sheehy MJ

    更新日期:1992-02-01 00:00:00

  • Pericyte Bridges in Homeostasis and Hyperglycemia.

    abstract::Diabetic retinopathy is a potentially blinding eye disease that threatens the vision of one-ninth of patients with diabetes. Progression of the disease has long been attributed to an initial dropout of pericytes that enwrap the retinal microvasculature. Revealed through retinal vascular digests, a subsequent increase ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db19-0471

    authors: Corliss BA,Ray HC,Doty RW,Mathews C,Sheybani N,Fitzgerald K,Prince R,Kelly-Goss MR,Murfee WL,Chappell J,Owens GK,Yates PA,Peirce SM

    更新日期:2020-07-01 00:00:00

  • Fibrinopeptide-A in diabetes mellitus. Relation to levels of blood glucose, fibrinogen disappearance, and hemodynamic changes.

    abstract::Plasma and urine fibrinopeptide-A (FPA) levels were investigated in type I and II diabetic patients. Plasma FPA and 24-h urinary excretion of FPA were significantly elevated in diabetic patients compared with normal volunteers, indicating augmented thrombin activity in diabetes. Plasma and urine FPA did not differ bet...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.9.836

    authors: Jones RL

    更新日期:1985-09-01 00:00:00

  • Apoptosis is the mode of beta-cell death responsible for the development of IDDM in the nonobese diabetic (NOD) mouse.

    abstract::The NOD/Lt mouse, a widely used model of human autoimmune IDDM, was used to establish the mode of beta-cell death responsible for the development of IDDM. Apoptotic cells were present within the islets of Langerhans in hematoxylin and eosin-stained sections of pancreases harvested from 3- to 18-week-old female NOD/Lt ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.46.5.750

    authors: O'Brien BA,Harmon BV,Cameron DP,Allan DJ

    更新日期:1997-05-01 00:00:00

  • Relationship between renal function and metabolic alterations in early streptozocin-induced diabetes in rats.

    abstract::To investigate the temporal relationship of diabetes-induced renal growth and its associated metabolic alterations to the early development of renal hyperfunction, parallel functional and metabolic studies were performed shortly after the onset of diabetes in rats. Hyperglycemia and hypoinsulinemia were evident 18 h a...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.36.1.80

    authors: Cortes P,Dumler F,Goldman J,Levin NW

    更新日期:1987-01-01 00:00:00

  • Hyperlipoproteinemia in streptozotocin-treated rats.

    abstract::In order to study hyperlipidemia in diabetes mellitus, rats were made diabetic by administration of streptozotocin and the optimal conditions for production of severe and persistent hyperlipoprotenemia determined. Two groups of rats were compared: rats fed sucrose-rich diets and rats fed laboratory chow. The optimal d...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.25.6.509

    authors: Bar-On H,Roheim PS,Eder HA

    更新日期:1976-06-01 00:00:00

  • A novel gene for neonatal diabetes maps to chromosome 10p12.1-p13.

    abstract::We report a genomewide linkage analysis of a large consanguineous family segregating autosomal recessively inherited neonatal diabetes and the identification of a novel neonatal diabetes locus. Neonatal diabetes was characterized by low levels of circulating C-peptide with very low to undetectable levels of insulin in...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.10.2636

    authors: Sellick GS,Garrett C,Houlston RS

    更新日期:2003-10-01 00:00:00

  • SRY-Box Containing Gene 4 Promotes Liver Steatosis by Upregulation of SREBP-1c.

    abstract::Obesity is usually associated with an increased risk of nonalcoholic fatty liver disease that is characterized by accumulation of excessive triglyceride (TG) in hepatocytes. However, the factors involved in the obesity-induced hepatosteatosis are poorly defined. Here, we report that SRY-box containing gene 4 (Sox4), a...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db18-0184

    authors: Jiao Y,Zhao J,Zhang Z,Li M,Yu X,Yang Y,Liu J,Liao S,Li D,Wang Y,Zhang D,Chen Y,Shi G,Liu B,Lu Y,Li X

    更新日期:2018-11-01 00:00:00

  • Acute bidirectional manipulation of muscle glucose uptake by in vivo electrotransfer of constructs targeting glucose transporter genes.

    abstract::Analysis of conventional germ-line or tissue-specific gene manipulation in vivo is potentially confounded by developmental adaptation of animal physiology. We aimed to adapt the technique of in vivo electrotransfer (IVE) to alter local gene expression in skeletal muscle of rodents as a means of investigating the role ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.9.2702

    authors: Cleasby ME,Davey JR,Reinten TA,Graham MW,James DE,Kraegen EW,Cooney GJ

    更新日期:2005-09-01 00:00:00

  • Modulation of adipose lipoprotein lipase by thyroid hormone and diabetes. The significance of the low T3 state.

    abstract::The present study was performed to assess the potential relationship between the low T3 syndrome and hypothyroidism. Comparative studies were performed on the relative effects of diabetes and insulin on heparin-releasable adipose lipoprotein lipase (LPL) in the intact and hypothyroid rat. Hypothyroidism for 10 days (T...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.12.1266

    authors: Gavin LA,McMahon F,Moeller M

    更新日期:1985-12-01 00:00:00

  • Mitogen-activated protein kinase p38 mediates reduced nerve conduction velocity in experimental diabetic neuropathy: interactions with aldose reductase.

    abstract::This study examined the role of p38 mitogen-activated protein (MAP) kinase in transducing high glucose into deficits in nerve conduction velocity (NCV) that are characteristic of diabetic neuropathy. p38 activation and NCV were measured in streptozocin-induced diabetic rats treated with a p38 inhibitor, an aldose redu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.7.1851

    authors: Price SA,Agthong S,Middlemas AB,Tomlinson DR

    更新日期:2004-07-01 00:00:00

  • The diabetogenic effects of streptozotocin in mice are prolonged and inversely related to age.

    abstract::Single "subdiabetogenic" doses of streptozotocin (SZ), when given to young male CD-1 mice, produced a delayed onset of hyperglycemia dependent on the dose of SZ and on the age of the mice. The effect was markedly reduced or absent in older mice given the same dose of SZ per kg of body weight. Histologic examination of...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.30.9.718

    authors: Riley WJ,McConnell TJ,Maclaren NK,McLaughlin JV,Taylor G

    更新日期:1981-09-01 00:00:00

  • Subclinical Disease Burden as Assessed by Whole-Body MRI in Subjects With Prediabetes, Subjects With Diabetes, and Normal Control Subjects From the General Population: The KORA-MRI Study.

    abstract::Detailed pathophysiological manifestations of early disease in the context of prediabetes are poorly understood. This study aimed to evaluate the extent of early signs of metabolic and cardio-cerebrovascular complications affecting multiple organs in individuals with prediabetes. Subjects without a history of stroke, ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db16-0630

    authors: Bamberg F,Hetterich H,Rospleszcz S,Lorbeer R,Auweter SD,Schlett CL,Schafnitzel A,Bayerl C,Schindler A,Saam T,Müller-Peltzer K,Sommer W,Zitzelsberger T,Machann J,Ingrisch M,Selder S,Rathmann W,Heier M,Linkohr B,Meisi

    更新日期:2017-01-01 00:00:00

  • Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer.

    abstract::The relationships between diabetes and pancreatic ductal adenocarcinoma (PDAC) are complex. Longstanding type 2 diabetes (T2DM) is a risk factor for pancreatic cancer, but increasing epidemiological data point to PDAC as also a cause of diabetes due to unknown mechanisms. New-onset diabetes is of particular interest t...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db16-1477

    authors: Andersen DK,Korc M,Petersen GM,Eibl G,Li D,Rickels MR,Chari ST,Abbruzzese JL

    更新日期:2017-05-01 00:00:00

  • Variation in the adiponutrin gene influences its expression and associates with obesity.

    abstract::Adiponutrin is one of three recently identified adipocyte lipases. Surprisingly, these proteins also retain transacylase activity, a hitherto unknown pathway of triacylglycerol synthesis in the adipocytes. This may enable them to participate in both anabolic and catabolic processes. The adiponutrin gene (ADPN) is down...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.55.03.06.db05-1075

    authors: Johansson LE,Hoffstedt J,Parikh H,Carlsson E,Wabitsch M,Bondeson AG,Hedenbro J,Tornqvist H,Groop L,Ridderstråle M

    更新日期:2006-03-01 00:00:00

  • Transplantation without immunosuppression.

    abstract::Exciting new findings have been reported in the past few years that indicate that islets can be transplanted successfully across major histocompatibility barriers without the continuous use of immunosuppressive agents by techniques designed to eliminate passenger leukocytes. In vitro culture of donor islets either at ...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/diab.31.4.s11

    authors: Faustman D,Lacy PE,Davie JM

    更新日期:1982-08-01 00:00:00

  • Anti-CD154 (CD40L) prevents recurrence of diabetes in islet isografts in the DR-BB rat.

    abstract::Islet transplantation for the treatment of autoimmune diabetes is more difficult because of the additional barrier presented by the autoimmunity. We tested the ability of hamster anti-rat CD154 to prevent recurrence of diabetes in renal subcapsular islet isografts in DR-BB (RT1uu) rats with established autoimmune diab...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.49.10.1666

    authors: Kover KL,Geng Z,Hess DM,Benjamin CD,Moore WV

    更新日期:2000-10-01 00:00:00

  • Mitochondrial DNA coding and control region variants as genetic risk factors for type 2 diabetes.

    abstract::Both the coding and control regions of mitochondrial DNA (mtDNA) play roles in the generation of diabetes; however, no studies have thoroughly reported on the combined diabetogenic effects of variants in the two regions. We determined the mitochondrial haplogroup and the mtDNA sequence of the control region in 859 sub...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-1369

    authors: Liou CW,Chen JB,Tiao MM,Weng SW,Huang TL,Chuang JH,Chen SD,Chuang YC,Lee WC,Lin TK,Wang PW

    更新日期:2012-10-01 00:00:00

  • Onset and progression of diabetic glomerulosclerosis; a prospective study based on serial renal biopsies.

    abstract::Clinical factors related to the development and progression of renal lesions were studied in twenty-three diabetics by the use of serial renal biopsies or autopsy. The results were as follows: Most of the juvenile and intermediate type diabetics were poorly controlled, with the glomerular lesion progressing rather rap...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.24.1.1

    authors: Takazakura E,Nakamoto Y,Hayakawa H,Kawai K,Muramoto S

    更新日期:1975-01-01 00:00:00

  • Studies on dehydrogenases of the glucuronate-xylulose cycle in the livers of diabetic mice and rats.

    abstract::In view of reports that accessory pathways of glucose oxidation are enhanced in the diabetic state, we have determined the levels of key enzymes of the glucuronate-xylulose cycle in the livers of diabetic mice and rats. Genetically diabetic mice (db/db) were found to have increased levels of two NADP-linked enzymes of...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.28.9.793

    authors: Tulsiani DR,Touster O

    更新日期:1979-09-01 00:00:00

  • Comparison of central and peripheral administration of C75 on food intake, body weight, and conditioned taste aversion.

    abstract::Mice respond to fatty acid synthase (FAS) inhibitors by profoundly reducing their food intake and body weight. Evidence indicates that the central nervous system (CNS) may be the critical site of action; however, a peripheral contribution cannot be ruled out. We compared doses of the FAS inhibitor C75 in the CNS (thir...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.11.3196

    authors: Clegg DJ,Wortman MD,Benoit SC,McOsker CC,Seeley RJ

    更新日期:2002-11-01 00:00:00

  • Effects of gestational hyperglycemia on glucose metabolism and its hormonal control in the fasted, newborn rat during the early postnatal period.

    abstract::To evaluate the effects of gestational hyperglycemia on glucose metabolism and its regulation in the fasted rat during the early postnatal period, unrestrained rats were continuously infused with glucose during the last week of pregnancy. Control rats were infused with distilled water. Newborns were studied during the...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.10.995

    authors: Nurjhan N,Ktorza A,Ferre P,Girard JR,Picon L

    更新日期:1985-10-01 00:00:00

  • Interleukin-18 promoter polymorphisms in type 1 diabetes.

    abstract::Type 1 diabetes is believed to be a Th1 lymphocyte-mediated disease, and both environmental and genetic factors play a role in its pathogenesis. It was recently found that interleukin (IL)-18 acts as a proinflammatory cytokine and, in synergy with IL-12, promotes development of Th1 lymphocyte response by induction of ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.11.3347

    authors: Kretowski A,Mironczuk K,Karpinska A,Bojaryn U,Kinalski M,Puchalski Z,Kinalska I

    更新日期:2002-11-01 00:00:00

  • β-Lapachone Prevents Diet-Induced Obesity by Increasing Energy Expenditure and Stimulating the Browning of White Adipose Tissue via Downregulation of miR-382 Expression.

    abstract::There has been great interest in the browning of fat for the treatment of obesity. Although β-lapachone (BLC) has potential therapeutic effects on obesity, the fat-browning effect and thermogenic capacity of BLC on obesity have never been demonstrated. Here, we showed that BLC stimulated the browning of white adipose ...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db15-1423

    authors: Choi WH,Ahn J,Jung CH,Jang YJ,Ha TY

    更新日期:2016-09-01 00:00:00

  • Altered energy balance causes selective changes in melanocortin-4(MC4-R), but not melanocortin-3 (MC3-R), receptors in specific hypothalamic regions: further evidence that activation of MC4-R is a physiological inhibitor of feeding.

    abstract::We have examined the effects of underfeeding and obesity on the density of hypothalamic melanocortin MC3 and MC4 receptors (MC3-R and MC4-R, respectively), which may mediate the hypophagic effects of alpha-melanocyte-stimulating hormone (MSH) in the rat. MC3-R and MC4-R were measured by quantitative autoradiography in...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.48.2.267

    authors: Harrold JA,Widdowson PS,Williams G

    更新日期:1999-02-01 00:00:00

  • Transgenic restoration of long-chain n-3 fatty acids in insulin target tissues improves resolution capacity and alleviates obesity-linked inflammation and insulin resistance in high-fat-fed mice.

    abstract:OBJECTIVE:The catabasis of inflammation is an active process directed by n-3 derived pro-resolving lipid mediators. We aimed to determine whether high-fat (HF) diet-induced n-3 deficiency compromises the resolution capacity of obese mice and thereby contributes to obesity-linked inflammation and insulin resistance. RE...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db10-0054

    authors: White PJ,Arita M,Taguchi R,Kang JX,Marette A

    更新日期:2010-12-01 00:00:00

  • Rac1 is a novel regulator of contraction-stimulated glucose uptake in skeletal muscle.

    abstract::In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin. Whether Rac1 is activated by muscle contraction and regulates contraction-induced glucos...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db12-0491

    authors: Sylow L,Jensen TE,Kleinert M,Mouatt JR,Maarbjerg SJ,Jeppesen J,Prats C,Chiu TT,Boguslavsky S,Klip A,Schjerling P,Richter EA

    更新日期:2013-04-01 00:00:00

  • Metformin prevents the development of chronic heart failure in the SHHF rat model.

    abstract::Insulin resistance is a recently identified mechanism involved in the pathophysiology of chronic heart failure (CHF). We investigated the effects of two insulin-sensitizing drugs (metformin and rosiglitazone) in a genetic model of spontaneously hypertensive, insulin-resistant rats (SHHF). Thirty SHHF rats were randomi...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-1132

    authors: Cittadini A,Napoli R,Monti MG,Rea D,Longobardi S,Netti PA,Walser M,Samà M,Aimaretti G,Isgaard J,Saccà L

    更新日期:2012-04-01 00:00:00