Short-term infusion of interleukin-6 does not induce insulin resistance in vivo or impair insulin signalling in rats.
OBJECTIVE
Interleukin-6 has been implicated in the insulin resistance associated with obesity and impaired glucose tolerance. Previous studies in vitro have shown that IL-6 rapidly (1-2 h) impairs cellular insulin signalling and action through an increased expression of suppressor of cytokine signalling (SOCS)-3. In the present study, IL-6 or saline was infused in rats that were simultaneously in a state of hyperinsulinaemia. Muscle, liver and adipose tissue were excised after 2 h to examine potential effects on insulin signalling or gene expression.


METHODS
The rats were infused with IL-6 or saline during a euglycaemic-hyperinsulinaemic clamp and the glucose infusion rate was measured after 90 to 120 min. Signal transducer and activator of transcription (STAT)3 phosphorylation and insulin-stimulated tyrosine phosphorylation of the insulin receptors and IRS were measured with immunoblotting and gene expression through real-time PCR.


RESULTS
No inhibitory effect of IL-6 on insulin-stimulated whole-body glucose uptake was seen in spite of high circulating levels of IL-6 (0.85+/-0.08 nmol/l). Tyrosine phosphorylation of the insulin receptors and IRS was also unchanged in the liver, skeletal muscles and adipose tissue. However, tyrosine phosphorylation of STAT3 was increased in all tissues, showing that IL-6 signalling was activated. IL-6 mRNA tended to increase, while GLUT4, peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) and adiponectin gene expression were unchanged.


CONCLUSIONS
Infusion of IL-6 for 120 min in rats during euglycaemic-hyperinsulinaemic conditions did not alter the effect of insulin on whole-body glucose homeostasis, plasma adiponectin levels or insulin signalling in target tissues. Thus, the acute effects of IL-6, associated with SOCS-3 induction, do not lead to whole-body insulin resistance. These data further underscore the importance of the chronic, and potentially tissue-specific effects of IL-6 on insulin signalling and action.
Rotter Sopasakis
V
V
The Lundberg Laboratory for Diabetes Research, Department of Internal Medicine, The Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital, 413 45 Göteborg, Sweden.
Larsson
B-M
BM
Johansson
A
A
Holmäng
A
A
Smith
U
U
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism; D007328:Insulin / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D016209:Interleukin-8 / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D001786:Blood Glucose; D007328:Insulin; D016209:Interleukin-8