Volume 48, Number 1, 105-112, DOI: 10.1007/s00125-004-1598-x

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European Association for the Study of Diabetes

Hormone-sensitive lipase is reduced in the adipose tissue of patients with type 2 diabetes mellitus: influence of IL-6 infusion

M. J. Watt, A. L. Carey, E. Wolsk-Petersen, F. B. Kraemer, B. Klarland Pedersen and M. A. Febbraio

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Abstract

Aims/hypothesis  

Type 2 diabetes mellitus is characterised by increased plasma NEFA and IL-6 concentrations, and IL-6 increases lipolysis in healthy men. We assessed the adipose tissue hormone-sensitive lipase (HSL) mRNA expression, protein expression and HSL activity in patients with type 2 diabetes mellitus, and determined the effect of IL-6 administration on these measures.

Methods  

Seven patients with type 2 diabetes mellitus (age 67±4 years, weight 87±7 kg) and six age- and weight-matched individuals visited the laboratory on two occasions. Subcutaneous adipose tissue biopsies and blood samples were obtained prior to and during 3 h of either saline or recombinant human IL-6 infusion.

Results  

HSL mRNA was reduced (p<0.05) by sim40% in type 2 diabetes mellitus relative to control subjects, while HSL protein expression showed a tendency to be decreased (35%, p=0.09). HSL activity averaged 8.87±1.25 and 6.91±1.20 nmol min–1 mg–1 protein for control and type 2 diabetic subjects respectively (p<0.05). IL-6 administration increased (p<0.05) HSL mRNA 2-fold at 60 min in both groups, whereas HSL protein and activity were unaffected by IL-6. Plasma insulin was elevated (p<0.05) in patients with type 2 diabetes mellitus at rest and was blunted (p<0.05) during IL-6 infusion in both groups. Plasma glucagon and cortisol were elevated (p<0.05) by IL-6 in both groups.

Conclusions/interpretation  

Our data demonstrate that basal HSL is decreased in patients with type 2 diabetes mellitus, and this may be a consequence of elevated plasma insulin levels. We have also shown that IL-6 administration increases HSL gene expression, although it exerted no effect on HSL protein and activity. This disparity between mRNA, protein and enzyme activity may be a function either of the marked alterations in the hormonal milieu induced by IL-6 administration and/or of post-transcriptional events.

Keywords  Adipose tissue - Gene expression - Hormone-sensitive lipase - Interleukin-6 - Type 2 diabetes mellitus

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