Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes

N M Harder-Lauridsen; R Krogh-Madsen; Jens Juul Holst; P. Plomgaard; L Leick; B K Pedersen; C P Fischer

doi:10.1152/ajpendo.00571.2013

Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes

N M Harder-Lauridsen, R Krogh-Madsen, Jens Juul Holst, P. Plomgaard, L Leick, B K Pedersen, C P Fischer

27 Citationer (Scopus)

Abstract

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/m(2), HbA1c 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 hyperinsulinemic-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.

Originalsprog	Engelsk
Tidsskrift	American Journal of Physiology: Endocrinology and Metabolism
Vol/bind	306
Udgave nummer	7
Sider (fra-til)	E769-78
Antal sider	10
ISSN	0193-1849
DOI	https://doi.org/10.1152/ajpendo.00571.2013
Status	Udgivet - 1 apr. 2014

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title = "Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes",

abstract = "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/m(2), HbA1c 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 hyperinsulinemic-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.",

keywords = "Aged, Calorimetry, Cross-Over Studies, Diabetes Mellitus, Type 2, Glucose, Glucose Clamp Technique, Hormones, Humans, Insulin Resistance, Interleukin-6, Male, Middle Aged, Placebos, Recombinant Proteins",

author = "Harder-Lauridsen, {N M} and R Krogh-Madsen and Holst, {Jens Juul} and P. Plomgaard and L Leick and Pedersen, {B K} and Fischer, {C P}",

year = "2014",

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doi = "10.1152/ajpendo.00571.2013",

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TY - JOUR

T1 - Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes

AU - Harder-Lauridsen, N M

AU - Krogh-Madsen, R

AU - Holst, Jens Juul

AU - Plomgaard, P.

AU - Leick, L

AU - Pedersen, B K

AU - Fischer, C P

PY - 2014/4/1

Y1 - 2014/4/1

N2 - 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/m(2), HbA1c 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 hyperinsulinemic-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.

AB - 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/m(2), HbA1c 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 hyperinsulinemic-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.

KW - Aged

KW - Calorimetry

KW - Cross-Over Studies

KW - Diabetes Mellitus, Type 2

KW - Glucose

KW - Glucose Clamp Technique

KW - Hormones

KW - Humans

KW - Insulin Resistance

KW - Interleukin-6

KW - Male

KW - Middle Aged

KW - Placebos

KW - Recombinant Proteins

U2 - 10.1152/ajpendo.00571.2013

DO - 10.1152/ajpendo.00571.2013

M3 - Journal article

C2 - 24473436

SN - 0193-1849

VL - 306

SP - E769-78

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

IS - 7

ER -

Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes

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