The cAMP-HMGA1-RBP4 system: a novel biochemical pathway for modulating glucose homeostasis

Eusebio Chiefari, Francesco Paonessa, Stefania Iiritano, Ilaria Le Pera, Dario Palmieri, Giuseppe Brunetti, Angelo Lupo, Vittorio Colantuoni, Daniela Foti, Elio Gulletta, Giovambattista De Sarro, Alfredo Fusco, Antonio Brunetti

We previously showed that mice lacking the high mobility group A1 gene (Hmga1-knockout mice) developed a type 2-like diabetic phenotype, in which cell-surface insulin receptors were dramatically reduced (below 10% of those in the controls) in the major targets of insulin action, and glucose intolerance was associated with increased peripheral insulin sensitivity. This particular phenotype supports the existence of compensatory mechanisms of insulin resistance that promote glucose uptake and disposal in peripheral tissues by either insulin-dependent or insulin-independent mechanisms. We explored the role of these mechanisms in the regulation of glucose homeostasis by studying the Hmga1-knockout mouse model. Also, the hypothesis that increased insulin sensitivity in Hmga1-deficient mice could be related to the deficit of an insulin resistance factor is discussed.