期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 306, 期 7, 页码 E769-E778出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00571.2013
关键词
insulin resistance; metabolism; humans; clamp technique; biopsy; muscle; skeletal; inflammation; signal transducer and activator of transcription 3; interleukin-6
资金
- Danish National Research Foundation [DNRF55]
- Trygfonden
- Danish Ministry of Science, Technology, and Innovation
- Danish Council for Strategic Research [09-067009, 09-075724]
- Capital Region of Denmark
Elevated interleukin-6 (IL-6) levels are associated with type 2 diabetes, but its role in glucose metabolism is controversial. We investigated the effect of IL-6 on insulin-stimulated glucose metabolism in type 2 diabetes patients and hypothesized that an acute, moderate IL-6 elevation would increase the insulin-mediated glucose uptake. Men with type 2 diabetes not treated with insulin [ n = 9, age 54.9 +/- 9.7 (mean +/- SD) yr, body mass index 34.8 +/- 6.1 kg/m2, HbA(1c) 7.0 +/- 1.0%] received continuous intravenous infusion with either recombinant human IL-6 (rhIL-6) or placebo. After 1 h with placebo or rhIL-6, a 3-h hyperin-sulinemic-isoglycemic clamp was initiated. Whole body glucose metabolism was measured using stable isotope-labeled tracers. Signal transducer and activator of transcription 3 (STAT3) phosphorylation and suppressor of cytokine signaling 3 (SOCS3) expression were measured in muscle biopsies. Whole body energy expenditure was measured using indirect calorimetry. In response to the infusion of rhIL-6, circulating levels of IL-6 (P < 0.001), neutrophils (P < 0.001), and cortisol (P < 0.001) increased while lymphocytes decreased (P < 0.01). However, IL-6 infusion did not change glucose infusion rate, rate of appearance, or rate of disappearance during the clamp. While IL-6 enhanced phosphorylation of STAT3 in skeletal muscle (P = 0.041), the expression of SOCS3 remained unchanged. Whole body oxygen uptake (P < 0.01) and expired carbon dioxide (P < 0.01) increased during rhIL-6 infusion. In summary, although IL-6 induced local and systemic responses, the insulin-stimulated glucose uptake was not affected. While different contributing factors may be involved, our results are in contrast to our hypothesis and previous findings in young, healthy men.
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