High sensitivity of beta-cell replication to the inhibitory effects of interleukin-1beta: modulation by adenoviral overexpression of IGF2 in rat islets.
Interleukin-1beta (IL1B) is an important contributor to the autoimmune destruction of beta-cells in type 1 diabetes, and it has been recently related to the development of type 2 diabetes. IGF2 stimulates beta-cell proliferation and survival. We have determined the effect of IL1B on beta-cell replication, and the potential modulation by IGF2 and glucose. Control-uninfected and adenovirus encoding for IGF2 (Ad-IGF2)-infected rat islets were cultured at 5.5 or 22.2 mmol/l glucose with or without 1, 10, 30, and 50 U/ml of IL1B. beta-Cell replication was markedly reduced by 10 U/ml of IL1B and was almost nullified with 30 or 50 U/ml of IL1B. Higher concentrations of IL1B were required to increase beta-cell apoptosis. Although IGF2 overexpression had a strong mitogenic effect on beta-cells, IGF2 could preserve beta-cell proliferation only in islets cultured with 10 U/ml IL1B, and had no effect with 30 and 50 U/ml of IL1B. In contrast, IGF2 overexpression induced a clear protection against IL1B-induced apoptosis, and higher concentrations of the cytokine were needed to increase beta-cell apoptosis in Ad-IGF2-infected islets. These results indicate that beta-cell replication is highly sensitive to the deleterious effects of the IL1B as shown by the inhibition of replication by relatively low IL1B concentrations, and the almost complete suppression of beta-cell replication with high IL1B concentrations. Likewise, the inhibitory effects of IL-beta on beta-cell replication were not modified by glucose, and were only modestly prevented by IGF2 overexpression, in contrast with the higher protection against IL1B-induced apoptosis afforded by glucose and by IGF2 overexpression.
Estil les
Elisabet
E
Laboratory of Diabetes and Experimental Endocrinology, Department of Clinical Sciences, IDIBELL-University of Barcelona, Feixa Llarga s/n 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
Téllez
Noèlia
N
Soler
Joan
J
Montanya
Eduard
E
D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D018014:Gene Transfer Techniques; D005947:Glucose / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew
D053583:Interleukin-1beta; D007335:Insulin-Like Growth Factor II; D005947:Glucose