TLR2/4 dependent and independent effects of the hepatokine fetuin-A in islets

Background and Aim: The nonalcoholic fatty liver displays an altered secretion of hepatokines. Notably, increased plasma levels of the hepatokine fetuin-A strongly predicts the incidence of type-2 diabetes in humans. Fetuin-A inhibits insulin receptor signaling and augments inflammation. Fatty acid-induced activation of TLR4 in adipocytes has been found to depend on fetuin-A. The present study examines effects of fetuin-A on pancreatic islet cell function. Methods: Mouse islets were cultured in medium supplemented with fetuin-A (0.6 µg/ml) or serum albumin and palmitate (60 µmol/l), for 1h or 24h. Changes in gen…