Hormone-sensitive lipase is reduced in the adipose tissue of patients with type 2 diabetes mellitus: influence of IL-6 infusion.
OBJECTIVE
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 approximately 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
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.
Watt
M J
MJ
School of Medical Sciences, RMIT University, PO Box 71, Bundoora, 3083, Australia. matthew.watt@rmit.edu.au
Carey
A L
AL
Wolsk-Petersen
E
E
Kraemer
F B
FB
Pedersen
B Klarland
BK
Febbraio
M A
MA
D000273:Adipose Tissue / Q000201:enzymology*; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006728:Hormones / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D008875:Middle Aged; D012333:RNA, Messenger; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007328:Insulin; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D002787:Sterol Esterase