scholarly journals Inhibition of insulin secretion from rat islets of Langerhans by interleukin-6. An effect distinct from that of interleukin-1

1990 ◽  
Vol 272 (1) ◽  
pp. 243-245 ◽  
Author(s):  
C Southern ◽  
D Schulster ◽  
I C Green
Keyword(s):  
Insulin Secretion ◽  
Islets Of Langerhans ◽  
Interleukin 6 ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Rat Islets ◽  
Factor Alpha ◽  
Rat Islets Of Langerhans

Glucose-induced insulin secretion from islets cultured in the presence of interleukin-6 (IL-6) for 12-24 h was inhibited to a similar extent as when islets were treated with interleukin-1 beta (IL-1 beta). However, unlike IL-1 beta, IL-6 did not potentiate insulin secretion during an acute (30 min) exposure of islets to the cytokine, nor did it inhibit DNA synthesis during a 24 h culture period. A 12 h pretreatment of islets with tumour necrosis factor-alpha (TNF-alpha) combined with IL-1 beta potentiated the inhibitory effect of IL-1 beta on secretion, such that 20 mM-glucose-induced insulin secretion was abolished. No synergistic inhibition of secretion was observed with TNF-alpha and IL-6. However, IL-1 beta and IL-6 were found to inhibit insulin secretion in an additive manner. These results suggest that IL-6 inhibits insulin secretion in a manner distinct from that of IL-1 beta, and that IL-6 is unlikely to mediate the inhibitory effects of IL-1 beta or TNF-alpha on rat islets of Langerhans.

Interleukin 1 is Potent Modulator of Insulin Secretion from Isolated Rat Islets of Langerhans

Diabetes ◽  
1987 ◽  
Vol 36 (8) ◽  
pp. 963-970 ◽  
Author(s):  
P. G. Comens ◽  
B. A. Wolf ◽  
E. R. Unanue ◽  
P. E. Lacy ◽  
M. L. McDaniel
Keyword(s):  
Insulin Secretion ◽  
Islets Of Langerhans ◽  
Interleukin 1 ◽  
Rat Islets ◽  
Isolated Rat Islets ◽  
Rat Islets Of Langerhans ◽  
Isolated Rat

Interleukin 1 is potent modulator of insulin secretion from isolated rat islets of Langerhans

Diabetes ◽  
1987 ◽  
Vol 36 (8) ◽  
pp. 963-970 ◽  
Author(s):  
P. G. Comens ◽  
B. A. Wolf ◽  
E. R. Unanue ◽  
P. E. Lacy ◽  
M. L. McDaniel
Keyword(s):  
Insulin Secretion ◽  
Islets Of Langerhans ◽  
Interleukin 1 ◽  
Rat Islets ◽  
Isolated Rat Islets ◽  
Rat Islets Of Langerhans ◽  
Isolated Rat

NF-IL6 and AP-1 cooperatively modulate the activation of the TSG-6 gene by tumor necrosis factor alpha and interleukin-1

1994 ◽  
Vol 14 (10) ◽  
pp. 6561-6569
Author(s):  
L Klampfer ◽  
T H Lee ◽  
W Hsu ◽  
J Vilcek ◽  
S Chen-Kiang
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Human Fibroblasts ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Normal Human ◽  
Factor Alpha ◽  
Necrosis Factor

Tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) activate transcription of the TSG-6 gene in normal human fibroblasts through a promoter region (-165 to -58) that encompasses an AP-1 and a NF-IL6 site. We show by deletion analysis and substitution mutagenesis that both sites are necessary for activation by TNF-alpha. Activation by IL-1 requires the NF-IL6 site and is enhanced by the AP-1 site. These results suggest that the NF-IL6 and AP-1 family transcription factors functionally cooperate to mediate TNF-alpha and IL-1 signals. Consistent with this possibility, IL-1 and TNF-alpha markedly increase the binding of Fos and Jun to the AP-1 site, and NF-IL6 activates the native TSG-6 promoter. Activation by NF-IL6 requires an intact NF-IL6 site and is modulated by the ratio of activator to inhibitor NF-IL6 isoforms that are translated from different in-frame AUGs. However, the inhibitor isoform can also bind to the AP-1 site and repress AP-1 site-mediated transcription. The finding that the inhibitor isoform antagonizes activation of the native TSG-6 promoter by IL-1 and TNF-alpha suggests that NF-IL6 has a physiologic role in these cytokine responses. Thus, the functionally distinct NF-IL6 isoforms cooperate with Fos and Jun to positively and negatively regulate the native TSG-6 promoter by TNF-alpha and IL-1.

Immunoprecipitation of a pertussis toxin substrate of the Go family from rat islets of Langerhans

1992 ◽  
Vol 12 (2) ◽  
pp. 95-100 ◽  
Author(s):  
Nicholas S. Berrow ◽  
Roger D. Hurst ◽  
Susan L. F. Chan ◽  
Noel G. Morgan
Keyword(s):  
Molecular Weight ◽  
Insulin Secretion ◽  
Adenylate Cyclase ◽  
G Protein ◽  
G Proteins ◽  
Islets Of Langerhans ◽  
Pertussis Toxin ◽  
Inhibitory Receptors ◽  
Rat Islets ◽  
Rat Islets Of Langerhans

Rat islets express a pertussis toxin sensitive G-protein involved in receptor-mediated inhibition of insulin secretion. This has been assumed previously to represent “Gi” which couples inhibitory receptors to adenylate cyclase. Incubation of islet G-proteins with32P-NAD and pertussis toxin resulted in the labelling of a band of molecular weight 40,000. This band was very broad and did not allow resolution of individual components. Incubation of the radiolabelled proteins with an anti-Go antiserum resulted in specific immunoprecipitation of a32P-labelled band. These results demonstrate that the complement of pertussis toxin sensitive G-proteins in rat islets includes Go.

Involvement of a NF-kappa B-like transcription factor in the activation of the interleukin-6 gene by inflammatory lymphokines

1990 ◽  
Vol 10 (2) ◽  
pp. 561-568
Author(s):  
H Shimizu ◽  
K Mitomo ◽  
T Watanabe ◽  
S Okamoto ◽  
K Yamamoto
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcriptional Activation ◽  
Interleukin 6 ◽  
Interleukin 1 ◽  
Tnf Alpha ◽  
Nuclear Factor ◽  
Nf Kappa B ◽  
Necrosis Factor Alpha ◽  
Mediators Of Inflammation

Interleukin-6 (IL-6) is one of the major mediators of inflammation, and its expression is inducible by the other inflammatory lymphokines, interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). We demonstrate that a common IL-6 promoter element, termed inflammatory lymphokine-responsive element (ILRE), is important for induction of IL-6 gene expression by IL-1 and TNF-alpha despite possible differences in the mechanisms of action of these lymphokines. Remarkably, the ILRE sequence, located between -73 to -63 relative to the mRNA cap site, is highly homologous to NF-kappa B transcription factor-binding motifs and binds an IL-1-TNF-alpha-inducible nuclear factor; the sequence specificities, binding characteristics, and subcellular localizations of this factor are indistinguishable from those of NF-kappa B. In addition, mutations of the ILRE sequence which impair the binding of this nuclear factor abolished the induction of IL-6 gene expression by IL-1 and TNF-alpha in vivo. These results indicate that a nuclear factor indistinguishable from NF-kappa B is involved in the transcriptional activation of the IL-6 gene by IL-1 and TNF-alpha.

Sign in / Sign up

Export Citation Format

Share Document