Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes

K Fosgerau, Pia Søndergaard Galle, T Hansen, A Albrechtsen, C de Lemos Rieper, Bente Klarlund Pedersen, L Kongskov Larsen, Allan Randrup Thomsen, O Pedersen, M Bagge Hansen, Adam Steensberg

26 Citationer (Scopus)

Abstract

Interleukin-6 (IL6) is critically involved in inflammation and metabolism. About 1% of people produce IL6 autoantibodies (aAb-IL6) that impair IL6 signaling in vivo. We tested the hypothesis that the prevalence of such aAb-IL6 is increased in type 2 diabetic patients and that aAb-IL6 plays a direct role in causing hyperglycemia. In humans, the prevalence of circulating high-affinity neutralizing aAb-IL6 was 2.5% in the type 2 diabetic patients and 1% in the controls (odds ratio 2.5, 95% confidence interval 1.2-4.9, P=0.01). To test for the role of aAb-IL6 in causing hyperglycemia, such aAb-IL6 were induced in mice by a validated vaccination procedure. Mice with plasma levels of aAb-IL6 similar to the 2.5% type 2 diabetic patients developed obesity and impaired glucose tolerance (area under the curve (AUC) glucose, 2056+/-62 vs 1793+/-62, P=0.05) as compared with sham-vaccinated mice, when challenged with a high-fat diet. Mice with very high plasma levels of aAb-IL6 developed elevated fasting plasma glucose (mM, 4.8+/-0.4 vs 3.3+/-0.1, P
OriginalsprogEngelsk
TidsskriftJournal of Endocrinology
Vol/bind204
Udgave nummer3
Sider (fra-til)265-73
Antal sider9
ISSN0022-0795
DOI
StatusUdgivet - 1 mar. 2010

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