High insulin-induced down-regulation of Erk-1/IGF-1R/FGFR-1 signaling is required for oxidative stress-mediated apoptosis of adipose-derived stem cells.

Early human evidence such as case series or small samples is exploring possible benefits.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Homeostasis of adipose tissue requires highly coordinated response between circulating factors and cell population. Human adult adipose-derived stem cells (ASCs) display multiple differentiation properties and are sensitive to insulin stimulation. Insulin resistance and high level of circulating insulin characterize patients with type 2 diabetes and obesity. At physiological concentration, insulin promoted proliferation and survival of ASCs in vitro, whereas high insulin level induced their dose-dependent proliferative arrest and apoptosis. Insulin-induced apoptotic commitment depended on the down-regulation of Erk-1, insulin growth factor-1 receptor (IGF-1R), and fibroblast growth factor receptor-1 (FGFR-1)-mediated signaling. Specific inhibition of Erk-1/2, IGF-1R, and FGFR activity promoted ASC apoptosis but did not increase insulin effects, whereas EGFR and ErbB2 inhibition potentiated insulin-induced apoptosis. FGFRs and EGFR inhibition reduced ASC adipogenic differentiation, whereas Erk-1/2 and IGF-1R inhibition was ineffective. Insulin-induced apoptosis associated to reactive oxygen species (ROS) accumulation and inhibition of NADPH oxidase 4 (Nox4) activity prevented ASC apoptosis. Moreover, specific inhibition of Erk-1/2, IGF-1R, and FGFR-1 activity promoted ROS generation and this effect was not cumulative with that of insulin alone. Our data indicate that insulin con

Evidence level

Early human evidence such as case series or small samples is exploring possible benefits.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.