Hyperglycaemic stress on fibroblasts: a study of the effects on murine NIH/3T3 cells exposed to exogenous carnosine.

Programme and Abstracts of the 68th National Congress of the Italian Physiological Society (Società Italiana di Fisiologia) (Abstract) Carnosine (β-Ala-L-his, CAR) is an endogenous dipeptide acknowledged to contribute to maintenance of intracellular homeostasis in vertebrate excitable tissues. CAR biochemical properties (e.g. antioxidant and antiglycating activity) account for CAR homeostatic function(s) in many dysregulated states, such as hyperglycaemia upsetting diabetes-targeted tissue/organ districts. In this view, CAR hypoglycaemic effects have been shown to be physiologically regulated in the peripheral nervous system. Previously, we reported responsiveness of CAR-regulating genes in peripheral nerves of hyperglycaemic mice; remarkably, this responsiveness is strongly enhanced in the nerve’s fibroblast component. Here, we identify variations in expression of genes responsible for biosynthesis, degradation and transmembrane transport of CAR in the NIH/3T3 model of murine fibroblasts exposed to a hyperglycaemic stress, in the presence or absence of extracellular CAR. In parallel, we detect functional protection against the stress induced by glucose excess due to CAR, which inhibits ROS production and apoptotic events, and preserves fibroblast proliferation. Overall, the in vitro cellular model mirrors the ex vivo evidence in the peripheral nerves of hyperglycaemic mice, highlighting the (patho)physiological impact of CAR homeostatic variations in diabetes-targeted tissues and, remarkably, in fibroblasts, for which a functional role of ‘sensors’ of hyperglycaemic impairment in tissues could be reckoned