Nicotinamide protects human beta cells against chemically-induced necrosis, but not against cytokine-induced apoptosis

被引:78
作者
Hoorens, A [1 ]
Pipeleers, D [1 ]
机构
[1] Free Univ Brussels, Diabet Res Ctr, B-1090 Brussels, Belgium
关键词
nicotinamide; cytokine; islet; insulin; apoptosis; diabetes;
D O I
10.1007/s001250051113
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Nicotinamide intervention trials are presently undertaken to prevent Type I (insulin-dependent) diabetes in high risk subjects. They are based on studies in rodents reporting nicotinamide protection against beta-cell injury in vitro and in vivo. This study examines whether nicotinamide can protect human beta cells in vitro. At concentrations (2 and 5 mmol/l) to protect rat beta cells against necrosis by streptozotocin or hydrogen peroxide, nicotinamide prevents hydrogen peroxide-induced necrosis of human beta cells. As with rat beta cells, nicotinamide fails to protect human beta cells against apoptosis induced by a combination of the cytokines interleukin-1 beta, interferon-gamma and tumour necrosis factor-alpha. In rat beta cells, nicotinamide (2 to 20 mmol/l) was also found to induce apoptosis, in particular during the days following its protection against necrosis; this cytotoxic effect was not observed with human beta cells. These data demonstrate that nicotinamide can protect human beta cells against radical-induced necrosis, but not against cytokine-induced apoptosis. This effect is not associated with a delayed apoptosis as in rat beta cells.
引用
收藏
页码:55 / 59
页数:5
相关论文
共 12 条
[1]   Cytokines induce deoxyribonucleic acid strand breaks and apoptosis in human pancreatic islet cells [J].
Delaney, CA ;
Pavlovic, D ;
Hoorens, A ;
Pipeleers, DG ;
Eizirik, DL .
ENDOCRINOLOGY, 1997, 138 (06) :2610-2614
[2]   NICOTINAMIDE DECREASES NITRIC-OXIDE PRODUCTION AND PARTIALLY PROTECTS HUMAN PANCREATIC-ISLETS AGAINST THE SUPPRESSIVE EFFECTS OF COMBINATIONS OF CYTOKINES [J].
EIZIRIK, DL ;
SANDLER, S ;
WELSH, N ;
BENDTZEN, K ;
HELLERSTROM, C .
AUTOIMMUNITY, 1994, 19 (03) :193-198
[3]   PREVENTION OR DELAY OF TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS IN CHILDREN USING NICOTINAMIDE [J].
ELLIOTT, RB ;
CHASE, HP .
DIABETOLOGIA, 1991, 34 (05) :362-365
[4]   Glucose promotes survival of rat pancreatic beta cells by activating synthesis of proteins which suppress a constitutive apoptotic program [J].
Hoorens, A ;
VandeCasteele, M ;
Kloppel, G ;
Pipeleers, D .
JOURNAL OF CLINICAL INVESTIGATION, 1996, 98 (07) :1568-1574
[5]   Implantation of standardized beta-cell grafts in a liver segment of IDDM patients: graft and recipient characteristics in two cases of insulin-independence under maintenance immunosuppression for prior kidney graft [J].
Keymeulen, B ;
Ling, Z ;
Gorus, FK ;
Delvaux, G ;
Bouwens, L ;
Grupping, A ;
Hendrieckx, C ;
Pipeleers-Marichal, M ;
Van Schravendijk, C ;
Salmela, K ;
Pipeleers, DG .
DIABETOLOGIA, 1998, 41 (04) :452-459
[6]  
LING Z, 1994, DIABETOLOGIA, V37, P15
[7]   Apoptosis is the mode of beta-cell death responsible for the development of IDDM in the nonobese diabetic (NOD) mouse [J].
OBrien, BA ;
Harmon, BV ;
Cameron, DP ;
Allan, DJ .
DIABETES, 1997, 46 (05) :750-757
[8]   THE PHARMACOKINETICS OF NICOTINAMIDE IN HUMANS AND RODENTS [J].
PETLEY, A ;
MACKLIN, B ;
RENWICK, AG ;
WILKIN, TJ .
DIABETES, 1995, 44 (02) :152-155
[9]   PANCREATIC B-CELLS POSSESS DEFENSE-MECHANISMS AGAINST CELL-SPECIFIC TOXICITY [J].
PIPELEERS, D ;
VANDEWINKEL, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (14) :5267-5271
[10]   LONG-TERM EFFECTS OF NICOTINAMIDE-INDUCED INHIBITION OF POLY(ADENOSINE DIPHOSPHATE-RIBOSE) POLYMERASE-ACTIVITY IN RAT PANCREATIC-ISLETS EXPOSED TO INTERLEUKIN-1-BETA [J].
REDDY, S ;
SALARILAK, N ;
SANDLER, S .
ENDOCRINOLOGY, 1995, 136 (05) :1907-1912