Adipocyte-derived extracellular vesicles from obese, but not lean, mice transferred functional insulinotropic protein cargo into pancreatic β-cells, significantly enhancing glucose-stimulated insulin secretion (p=0.0047).
Adipocyte-derived extracellular vesicles from obese mice transfer insulinotropic proteins to pancreatic β-cells, amplifying insulin secretion to compensate for insulin resistance.
valor p: p=0.0047
Adipocyte-derived extracellular vesicles (AdEVs) are membranous nanoparticles that convey communication from adipose tissue to other organs. Here, to delineate their role as messengers with glucoregulatory nature, we paired fluorescence AdEV-tracing and SILAC-labeling with (phospho)proteomics, and revealed that AdEVs transfer functional insulinotropic protein cargo into pancreatic β-cells. Upon transfer, AdEV proteins were subjects for phosphorylation, augmented insulinotropic GPCR/cAMP/PKA signaling by increasing total protein abundances and phosphosite dynamics, and ultimately enhanced 1st-phase glucose-stimulated insulin secretion (GSIS) in murine islets. Notably, insulinotropic effects were restricted to AdEVs isolated from obese and insulin resistant, but not lean mice, which was consistent with differential protein loads and AdEV luminal morphologies. Likewise, in vivo pre-treatment with AdEVs from obese but not lean mice amplified insulin secretion and glucose tolerance in mice. This data suggests that secreted AdEVs can inform pancreatic β-cells about insulin resistance in adipose tissue in order to amplify GSIS in times of increased insulin demand.
Kulaj et al. (Thu,) conducted a other in Obesity and insulin resistance. Adipocyte-derived extracellular vesicles (AdEVs) from diet-induced obese mice vs. Vehicle or AdEVs from lean mice was evaluated on Glucose-stimulated insulin secretion (GSIS) (p=0.0047). Adipocyte-derived extracellular vesicles from obese, but not lean, mice transferred functional insulinotropic protein cargo into pancreatic β-cells, significantly enhancing glucose-stimulated insulin secretion (p=0.0047).