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.
引用
收藏
页码:311 / 318
页数:8
相关论文
共 30 条
[1]  
Eisenbarth G.S., Type 1 diabetes mellitus: a chronic autoimmune disease, N Eng J Med, 314, pp. 1360-1368, (1986)
[2]  
Junker K., Egeberg J., Kromann H., Nerup J., An autopsy study of the islets of Langerhans in acute-onset juvenile diabetes mellitus, Acta Pathol Microbiol Scand(Sect A), 85, pp. 699-706, (1977)
[3]  
Foulis A.K., Farquharson M.A., Hardman R., Aberrant expression of class II major histocompatibility complex molecules by β cells and hyperexpression of class I major histocompatibility complex molecules by insulin containing islets in type I (insulin-dependent) diabetes mellitus, Diabetalogia, 30, pp. 333-343, (1987)
[4]  
Nerup J., Mandrup-Poulsen T., Molvig J., Helqvist S., Wogensen L.D., Egeberg J., Mechanisms of pancreatic β-cell destruction in Type I diabetes, Diabetes Care, 11, pp. 16-23, (1988)
[5]  
Blom L., Nystrom L., Sandstrom A., Dahlquist G., Infections and vaccinations as risk determinants for diabetes in childhood, Acta Endocrinol (Copenh), 122, (1990)
[6]  
Wogensen L., Reimers J., Heding L., Nerup J., Interleukin-1-beta (IL-1) is diabetogenic in normal rats, Diabetes, 39, (1990)
[7]  
Cyclosporin-induced remission of IDDM after early intervention. Association of 1 yr of cyclosporin treatment with enhanced insulin secretion, Diabetes, 37, pp. 1574-1582, (1988)
[8]  
Eizirik D.L., Strandell E., Bendtzen K., Sandier S., Functional characteristics of rat pancreatic islets maintained in culture after exposure to human interleukin 1, Diabetes, 38, pp. 16-19, (1988)
[9]  
Brunstedt J., Nielsen J.H., Isolation of islets from mice and rats, Methods in Diabetes Research, 1, pp. 254-258, (1984)
[10]  
Palmer J.P., Helqvist S., Spinas G.A., Molvig J., Mandrup-Poulsen T., Andersen H.U., Nerup J., Interaction of β-cell activity and IL-1 concentration and exposure time in isolated rat islets of Langerhans, Diabetes, 38, pp. 1211-1216, (1989)