REPETITIVE EXPOSURE OF PANCREATIC-ISLETS TO INTERLEUKIN-1-BETA - AN INVITRO MODEL OF PREDIABETES

被引:20
作者
HELQVIST, S [1 ]
ZUMSTEG, UW [1 ]
SPINAS, GA [1 ]
PALMER, JP [1 ]
MANDRUPPOULSEN, T [1 ]
EGEBERG, J [1 ]
NERUP, J [1 ]
机构
[1] STENO MEM HOSP,NIELS STEENSENS VEJ 2,DK-2820 GENTOFTE,DENMARK
关键词
ISLETS OF LANGERHANS; INTERLEUKIN-1-BETA; INSULIN-DEPENDENT DIABETES-MELLITUS; GLUCAGON;
D O I
10.3109/08916939109001905
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The slowly progressing loss of glucose tolerance over years before clinical onset of Type 1 (insulin-dependent) diabetes mellitus may be due to repetitive immunological attacks on the pancreatic beta-cell mass. Accordingly, we studied the effects of repetitive exposure of isolated rat pancreatic islets to the beta-cytotoxic immune-mediator interleukin-1β Islets were exposed thrice to 60 U/ml of recombinant interleukin-1β for 24 hr. The islets were allowed to recover for 6 d between the interleukin-1β exposure periods. After each of the three interleukin-1β exposure periods, islet capacity to release insulin was decreased to 12, 6 and 3% of control, respectively, and islet insulin content decreased to 75, 56 and 21%, respectively. After the two recovery culture periods, the capacity for insulin release reversed to 75 and 30% of control, respectively. An increase in islet insulin content was only seen after the first recovery culture. During repetitive as well as long-term (6 d) interleukin-1β exposure of islets, medium accumulation of glucagon was either increased or unaffected. In analogy, beta-cells exposed to interleukin-1β for 6 d showed ultrastructural signs of degeneration and cytolysis, whereas alpha-cells were intact. In conclusion, interleukin-1β injury to beta-cells was partially reversible, but successive episodes of islet interleukin-1β exposure were increasingly detrimental; alpha-cell function and structure did not show susceptibility to damage by interleukin-1β These findings may contribute to our understanding of islet cell behaviour before and during onset of Type 1 diabetes. © 1991 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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页码:311 / 318
页数:8
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