INTERLEUKIN-6 - A FUNCTIONAL AND STRUCTURAL INVITRO MODULATOR OF BETA-CELLS FROM ISLETS OF LANGERHANS

被引：44

作者：

BUSCHARD, K ^{[1
]}

AAEN, K ^{[1
]}

HORN, T ^{[1
]}

VANDAMME, J ^{[1
]}

BENDTZEN, K ^{[1
]}

机构：

[1] KOMMUNE HOSP COPENHAGEN,BARTHOLIN INST,COPENHAGEN,DENMARK

来源：

AUTOIMMUNITY | 1990年 / 5卷 / 03期

关键词：

Electron microscopy; Insulin-dependent diabetes mellitus; Interleukin; 1; 6; Pancreatic islets of Langerhans; Ultrastructure;

D O I：

10.3109/08916939009002977

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 direct in vitro effect of interleukin-6 (IL-6) on pancreatic beta-cells was studied using isolated Lewis rat islets (25/ml/well) precultured for 7 days and then incubated with or without human recombinant 1L-6 (rIL-6) or purified human natural IL-6 (nlL-6). Both sources of IL-6 stimulated insulin secretion over a period of 6 days (P < 0.01). whereas the levels of insulin within the islets were unaffected. At concentrations above 1.5ng/ml, rIL-6 almost doubled the content of insulin in the supernatants. At an intermediate concentration, 0.5ng/ml, rIL-6 preserved insulin secretion by islets cocultured with 2ng/ml of human recombinant interleukin lβ (rIL-Iβ which otherwise inhibited insulin secretion to 60% of islets cultured in medium alone. Electron microscopic studies showed that rIL-6, 1.5ng/ml, caused beta-cell specific degenerative changes similar to those previously described after treatment with IL-1β; i.e. appearance of opaque intracytoplasmic bodies, autophage vacuoles and signs of mitochondrial degeneration. We conclude that human IL-6 stimulates insulin production and secretion in virro and induces similar ultrastructural changes in beta-cells as does IL-Iβ IL-6 may be an endogenous mediator of some of the effects on beta-cells ascribed to IL-1. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

引用

页码：185 / 194

页数：10

共 35 条

[1]

Bendtzen K., Mandrup-Poulsen T., Nerup J., Nielsen J.H., Dinarello C.A., Svenson M., Human PI 7 interleukin 1 is cytotoxic for pancreatic islets of Langerhans, Science, 232, pp. 1545-1547, (1986)

[2]

Zawalich W.S., Diaz V.A., Interleukin 1 inhibits insulin secretion from isolated perifused rat islets, Diabetes, 35, 11, pp. 19-1123, (1986)

[3]

Sandler S., Anderson A., Hellerstrom C., Inhibitory effects of interleukin I on insulin secretion, insulin biosynthesis, and oxidative metabolism of isolated rat pancreatic islets, Endocrinol, 121, pp. 1424-1431, (1987)

[4]

Comens P.G., Wolf B.A., Unanue E.R., Lacy P.E., McDaniel M.L., Interleukin I is potent modulator of insulin secretion from isolated rat islets of Langerhans, Diabetes, 36, pp. 963-970, (1987)

[5]

del Rey A., Besedovsky H., Interleukin 1 affects glucose homeostasis, Am J Physiol, 253, pp. R794-R798, (1987)

[6]

Pukel C., Baquerizo H., Rabinovitch A., Destruction of rat islet cell monolayers by cytokines. Synergis-tic interactions of interferon-gamma, tumor necrosis factor, lymphotoxin, and interleukin 1, Diabetes, 37, pp. 133-136, (1988)

[7]

Cornell R.P., Schwartz D.B., Central administration of interleukin 1 elicits hyperinsulinemia in rats, Am J Physiol, 256, pp. R772-R777, (1989)

[8]

Mandrup-Poulsen T., Egeberg J., Nerup J., Bendtzen K., Nielsen J.H., Dinarello C.A., Ultrastructural studies of time-course and cellular specificity of interleukin-I mediated islet cytotoxicity, Acta Pathol Microbiol Immunol Scand Sect C, 95, pp. 55-63, (1987)

[9]

Sandler S., Bendtzen K., Borg L.A.H., Eizirik D.L., Strandell E., Welsh N., Studies on the mechanisms causing inhibition of insulin secretion in rat pancreatic islets exposed to human interleukin-ID indicate a perturbation in the mitochondrial function, Endocrinology, 124, pp. 1492-1501, (1989)

[10]

Mandrup-Poulsen T., Bendtzen K., Dinarello C.A., Nerup J., Human tumor necrosis factor potentiates human interleukin-I mediated rat pancreatic-cell cytotoxicity, J Immunol, 139, pp. 4077-4082, (1988)

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