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

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 similar to 40% 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.