Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans - PubMed (original) (raw)

Clinical Trial

Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans

Adam Steensberg et al. J Physiol. 2003.

Abstract

The cytokine interleukin (IL)-6 has recently been linked with type 2 diabetes mellitus and has been suggested to affect glucose metabolism. To determine whether acute IL-6 administration affects whole-body glucose kinetics or muscle glucose uptake, 18 healthy young men were assigned to one of three groups receiving a high dose of recombinant human IL-6 (HiIL-6; n = 6), a low dose of IL-6 (LoIL-6; n = 6) or saline (Con; n = 6) infused into one femoral artery for 3 h. The stable isotope [6,6-2H2] glucose was infused into a forearm vein throughout the 3 h infusion period and for a further 3 h after the cessation of infusion (recovery) to determine endogenous glucose production and whole-body glucose disposal. Infusion with HiIL-6 and LoIL-6 resulted in a marked (P < 0.05) increase in systemic IL-6 concentration throughout the 3 h of infusion (mean arterial plasma [IL-6]s of 319 and 143 pg ml-1 for HiIL-6 and LoIL-6, respectively), followed by a rapid decline (P < 0.05) during the recovery period. Subjects experienced clinical symptoms such as shivering and discomfort during HiIL-6 administration, but were asymptomatic during LoIL-6 administration. In addition, only HiIL-6 elevated (P < 0.05) plasma adrenaline (epinephrine). IL-6 infusion, irrespective of dose, did not result in any changes to endogenous glucose production, whole-body glucose disposal or leg- glucose uptake. These data demonstrate that acute IL-6 administration does not impair whole-body glucose disposal, net leg-glucose uptake, or increase endogenous glucose production at rest in healthy young humans.

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Figures

Figure 1

Figure 1. Effect of infusion of high and low doses of recombinant human interleukin-6 (rhIL-6) on arterial and venous plasma [IL-6] and net differences in [IL-6]

Arterial plasma [IL-6 ](_A_), venous plasma [IL-6] from the infusion leg (INFLEG) (B) and net [IL-6] differences in the systemic leg (SYSLEG) (C) during and after 3 h infusion of saline, a low or a high dose of rhIL-6 (Con, LoIL-6 and HiIL-6, respectively). Data are presented as means ±

s.e.m.

(n = 6). # Significantly different from Con (P < 0.05); $ Significantly different from LoIL-6 (P < 0.05).

Figure 3

Figure 3. Effect of infusion of high and low doses of rhIL-6 on arterial glucose concentration and net leg-glucose uptake in the infusion leg

Arterial glucose concentration (A) and net leg-glucose uptake in the infusion leg (B) before, during and after 3 h infusion of saline, a low or a high dose of rhIL-6. Data are presented as means ±

s.e.m.

(n = 6).

Figure 2

Figure 2. Effect of infusion of high and low doses of rhIL-6 on the rate of appearance (Ra) and disappearance (Rd) of 6,6-2H glucose, and on the metabolic clearance rate (MCR)

[6, 6-2H] glucose Ra (A), Rd (B) and MCR (C) before (Pre), during and after 3 h infusion of saline, a low or a high dose of rhIL-6. Data are presented as means ±

s.e.m.

(n = 6). § Time effect for Con, LoIL-6 and HiIL-6 (P < 0.05).

Figure 5

Figure 5. Effects of infusion of high and low doses of rhIL-6 on muscle GLUT 4 mRNA

Muscle GLUT 4 mRNA/28S rRNA before, during and after 3 h infusion of saline, a low or a high dose of rhIL-6. Data are presented as geometric means ±

s.e.m.

(n = 6). # Significantly different from pre-infusion for Con, LoIL-6 and HiIL-6 (P < 0.05).

Figure 4

Figure 4. Effects of infusion of high and low doses of rhIL-6 on muscle glycogen content

Muscle glycogen content in the infusion leg before, during and after 3 h infusion of either saline, a low or a high dose of rhIL-6. Data are presented as means +

s.e.m.

(n = 6).

Figure 7

Figure 7. Effects of infusion of high and low doses of rhIL-6 on plasma levels of noradrenaline and adrenaline

Plasma levels of noradrenaline (A) and adrenaline (B) before, during and after 3 h infusion of saline, a low or a high dose of rhIL-6. Data are presented as means ±

s.e.m.

(n = 6). # Significantly different from Con (P < 0.05).

Figure 6

Figure 6. Effects of infusion of high and low doses of rhIL-6 on plasma levels of insulin, glucagon and cortisol

Plasma insulin (A), glucagon (B) and cortisol (C) before, during and after 3 h infusion of saline, a low or a high dose of rhIL-6. Data are presented as means ±

s.e.m.

(n = 6). § Time effect for Con, LoIL-6 and HiIL-6 (P < 0.05). * Significantly different from Pre (P < 0.05). # Significantly different from Con (P < 0.05). $ Significantly different from LoIL-6 (P < 0.05).

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