NICOTINAMIDE DECREASES NITRIC-OXIDE PRODUCTION AND PARTIALLY PROTECTS HUMAN PANCREATIC-ISLETS AGAINST THE SUPPRESSIVE EFFECTS OF COMBINATIONS OF CYTOKINES

被引：43

作者：

EIZIRIK, DL

SANDLER, S

WELSH, N

BENDTZEN, K

HELLERSTROM, C

机构：

[1] Department of Medical Cell Biology, Uppsala University, Uppsala

[2] Laboratory of Medical Immunology, Medical Department TTA, University Hospital, Copenhagen

来源：

AUTOIMMUNITY | 1994年 / 19卷 / 03期

关键词：

PANCREATIC ISLETS; NITRIC OXIDE; NICOTINAMIDE; INTERLEUKIN-1-BETA; TUMOR NECROSIS FACTOR-ALPHA; INTERFERON-GAMMA; INSULIN RELEASE;

D O I：

10.3109/08916939408995694

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

It has been recently reported that human pancreatic islets in tissue culture produce nitric oxide (NO) and show a decreased function when exposed for 6 days to combinations of cytokines (interleukin-1 beta (IL-1 beta)+ tumor necrosis factor-alpha (TNF-alpha)+ interferon-gamma (IFN-gamma). Here we study the effects of nicotinamide (Nic; 10 or 20 mmol/l) on these deleterious effects of cytokines (50 U/ml IL-1 beta + 1000 U/ml TNF-alpha+ 1000 U/ml IFN-gamma). Islets were isolated from 8 human pancreata at the Central Unit of the P-cell Transplant, Brussels, sent to Uppsala and, after 3-5 days in culture, exposed for 6 additional days to the cytokines and/or Nic. The cytokines induced a 6-fold increase in islet NO production (P < 0.001), and this effect was partially counteracted by Nic (50-60% decrease in NO production; P < 0.001). The cytokines severely decreased the islet insulin content and glucose-induced insulin release (16.7 mmol/l glucose; 90% decrease; P < 0.001). Both these effects of cytokines were partially counteracted by Nic, especially at the highest concentration (20 mmol/l; 2-4-fold increase compared to islets exposed to cytokines alone; P < 0.01). Nic by itself did not affect the insulin content or insulin release by control islets. In conclusion, the present data indicate that Nic counteracts the deleterious effects of cytokines on human pancreatic islets. This effect of Nic may be relevant for the beneficial effects of the drug in early IDDM.

引用

页码：193 / 198

页数：6

共 33 条

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