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Peroxisome proliferator‐activated receptor γ (PPAR) agonism reduces the insulin‐stimulated increase in circulating interleukin‐6 in GH replaced GH‐deficient adults
Author(s) -
Krag Morten B.,
Rasmussen Lars M.,
Hansen Troels K.,
Frystyk Jan,
Flyvbjerg Allan,
Møller Niels,
Jørgensen Jens O. L.
Publication year - 2009
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.2008.03483.x
Subject(s) - medicine , endocrinology , agonist , insulin resistance , peroxisome proliferator activated receptor , insulin , inflammation , pioglitazone , receptor , diabetes mellitus , biology , type 2 diabetes
Summary Context Peroxisome proliferator‐activated receptor γ (PPARγ) agonists modify cardiovascular risk factors and inflammatory markers in patients with type 2 diabetes. GH treatment in GH‐deficient (GHD) patients may cause insulin resistance and exerts ambiguous effects on inflammatory markers. Objective To investigate circulating markers of inflammation and endothelial function in GH replaced GHD patients before and after 12 weeks administration of either pioglitazone 30 mg/day ( N = 10) or placebo ( N = 10) in a randomized double‐blind parallel design. Methods Circulating levels of interleukins (ILs)‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, tumour necrosis factor (TNF)‐α, high sensitivity C‐reactive protein, vascular cell adhesion molecule‐I, and osteoprotegerin (OPG) were measured in the basal state and after a 2·5 h hyperinsulinaemic euglycaemic clamp. Results Insulin sensitivity improved in the group receiving PPARγ agonist ( P = 0·03). Serum IL‐6 levels increased by 114 ± 31% (mean ± SE) in the entire group ( N = 20) following the hyperinsulinaemic euglycaemic clamp ( P = 0·01) performed at study start. Twelve weeks of PPARγ agonist treatment significantly abrogated this insulin‐stimulated increment in IL‐6 levels compared to placebo ( P = 0·01). Furthermore PPARγ agonist treatment significantly lowered basal IL‐4 levels ( P < 0·05). Conclusions (i) IL‐6 levels increase during a hyperinsulinaemic clamp in GH replaced patients (ii) This increase in IL‐6 is abrogated by PPARγ agonist treatment (iii) we hypothesize that PPARγ agonist‐induced improvement of insulin sensitivity may obviate a compensatory rise in IL‐6.