Interleukin 6: a functional and structural in vitro modulator of beta-cells from islets of Langerhans.
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 IL-6 (rIL-6) or purified human natural IL-6 (nIL-6). Both sources of IL-6 stimulated insulin secretion over a period of 6 days (P less than 0.01), whereas the levels of insulin within the islets were unaffected. At concentrations above 1.5 ng/ml, rIL-6 almost doubled the content of insulin in the supernatants. At an intermediate concentration, 0.5 ng/ml, rIL-6 preserved insulin secretion by islets cocultured with 2 ng/ml of human recombinant interleukin 1 beta (rIL-1 beta) which otherwise inhibited insulin secretion to 60% of islets cultured in medium alone. Electron microscopic studies showed that rIL-6, 1.5 ng/ml, caused beta-cell specific degenerative changes similar to those previously described after treatment with IL-1 beta; 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 vitro and induces similar ultrastructural changes in beta-cells as does IL-1 beta. IL-6 may be an endogenous mediator of some of the effects on beta-cells ascribed to IL-1.
Buschard
K
K
Bartholin Institute, Kommunehospitalet, Copenhagen, Denmark.
Aaen
K
K
Horn
T
T
Van Damme
J
J
Bendtzen
K
K
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology; D066298:In Vitro Techniques; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology; D015850:Interleukin-6 / Q000494:pharmacology* / Q000502:physiology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011917:Rats, Inbred Lew
D007328:Insulin; D007375:Interleukin-1; D015850:Interleukin-6