Figure 7.

Schematic presentation of the hypothetical local role of G-CSF in insulin resistance. In human skeletal muscle cells, saturated long-chain fatty acids (SFAs) activate, via Toll-like receptor 4 (TLR4)-dependent and -independent pathways, stress kinases and, further downstream, transcription factors (Rel-A, AP-1, C/EBPα) involved in the combinatorial induction of the G-CSF gene. Enhanced G-CSF production and release provokes, in an auto-/paracrine way, impairments of insulin actions in myocytes and the adjacent adipocytes of the so-called extramyocellular fat depot. Based on the mass of skeletal muscle and its surrounding fat depot, it is conceivable that this local insulin resistance contributes to whole-body insulin resistance.