Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Endocrinology |
| Vol/bind | 204 |
| Udgave nummer | 3 |
| Sider (fra-til) | 265-73 |
| Antal sider | 9 |
| ISSN | 0022-0795 |
| DOI | |
| Status | Udgivet - 1 mar. 2010 |
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Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes. / Fosgerau, K; Galle, P; Hansen, T; Albrechtsen, A; Rieper, C de Lemos; Pedersen, B Klarlund; Larsen, L Kongskov; Thomsen, A Randrup; Pedersen, O; Hansen, M Bagge; Steensberg, A; Fosgerau, K; Galle, Pia Søndergaard; Hansen, T; Albrechtsen, A; Rieper, C de Lemos; Pedersen, Bente Klarlund; Larsen, L Kongskov; Thomsen, Allan Randrup; Pedersen, O; Hansen, M Bagge; Steensberg, Adam.
I: Journal of Endocrinology, Bind 204, Nr. 3, 01.03.2010, s. 265-73.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes
AU - Fosgerau, K
AU - Galle, P
AU - Hansen, T
AU - Albrechtsen, A
AU - Rieper, C de Lemos
AU - Pedersen, B Klarlund
AU - Larsen, L Kongskov
AU - Thomsen, A Randrup
AU - Pedersen, O
AU - Hansen, M Bagge
AU - Steensberg, A
AU - Fosgerau, K
AU - Galle, Pia Søndergaard
AU - Hansen, T
AU - Albrechtsen, A
AU - Rieper, C de Lemos
AU - Pedersen, Bente Klarlund
AU - Larsen, L Kongskov
AU - Thomsen, Allan Randrup
AU - Pedersen, O
AU - Hansen, M Bagge
AU - Steensberg, Adam
PY - 2010/3/1
Y1 - 2010/3/1
N2 - 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<0.001) and impaired glucose tolerance (AUC glucose, 1340+/-38 vs 916+/-25, P<0.001) as compared with sham-control mice on normal chow. In conclusion, the prevalence of plasma aAb-IL6 at levels known to impair IL6 signaling in vivo is increased 2.5-fold in people with type 2 diabetes. In mice, matching levels of aAb-IL6 cause obesity and hyperglycemia. These data suggest that a small subset of type 2 diabetes may in part evolve from an autoimmune attack against IL6.
AB - 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<0.001) and impaired glucose tolerance (AUC glucose, 1340+/-38 vs 916+/-25, P<0.001) as compared with sham-control mice on normal chow. In conclusion, the prevalence of plasma aAb-IL6 at levels known to impair IL6 signaling in vivo is increased 2.5-fold in people with type 2 diabetes. In mice, matching levels of aAb-IL6 cause obesity and hyperglycemia. These data suggest that a small subset of type 2 diabetes may in part evolve from an autoimmune attack against IL6.
U2 - 10.1677/JOE-09-0413
DO - 10.1677/JOE-09-0413
M3 - Journal article
C2 - 20016056
VL - 204
SP - 265
EP - 273
JO - Journal of Endocrinology
JF - Journal of Endocrinology
SN - 0022-0795
IS - 3
ER -