Type 2 diabetes and
obesity are associated with an enhanced release of a number of
adipocytokines.
Hyperinsulinemia, frequently present in
type 2 diabetes and
obesity, might be one of the drivers of the enhanced production of
adipocytokines. The aim of this study was to investigate the interstitial levels of
cytokines in subcutaneous adipose tissue (SCAT) in response to
hyperinsulinemia and the effect of weight-reducing hypocaloric diet on this regulation in obese subjects. Thirteen obese premenopausal women participated in the study. Concentrations of seven
cytokines were measured in plasma and in AT interstitial fluid collected by microdialysis during a euglycemic-hyperinsulinemic clamp and during control infusion of physiological saline. A subgroup of six women underwent a 4-wk very-
low-calorie diet (VLCD). Microdialysis during the clamp was performed before and at the end of VLCD.
Hyperinsulinemia induced an increase of monocyte chemoatractant
protein (MCP-1) and
IL-6 SCAT interstitial and plasma levels and elevated
IL-8 levels in SCAT. The relative changes of
IL-6 levels in the
dialysate correlated with changes of
IL-8 and MCP-1. The interstitial and plasma levels of IL-1β,
IL-10, TNFα, and
plasminogen activator inhibitor (PAI-1) remained unchanged in response to
hyperinsulinemia. VLCD resulted in enhancement of the
hyperinsulinemia-induced augmentation of MCP-1,
IL-6, and
IL-8 interstitial levels. In conclusion,
hyperinsulinemia upregulates the interstitial levels of MCP-1,
IL-6, and
IL-8 in SCAT in obese women, whereas it does not affect IL-1β,
IL-10, TNFα, and
PAI-1 levels. Hypocaloric diet associated with
weight reduction enhances the
hyperinsulinemia-induced upregulation of MCP-1,
IL-6, and
IL-8 in SCAT.