Wei-Chiang Shen,
University of Southern Califonia, USA
Title: Proinsulin-transferrin fusion protein: An insulin analog to achieve both livertargeting and overcoming insulin resistance
Biography
Biography: Wei-Chiang Shen,
Abstract
We have recently prepared a recombinant proinsulin-transferrin fusion protein (ProINS-Tf). ProINS-Tf is an inactive form of insulin analog, but can be selectively absorbed, activated, and retained in the liver. We have demonstrated in type 1 diabetes mouse models that ProINS-Tf is a highly liver-targeted and long-lasting insulin prodrug. Due to the binding to both insulin and transferrin receptor, the liver-activated ProINS-Tf exhibited a significantly higher affinity to insulin receptor when compared with the native insulin. The bivalent binding of activated ProINS-Tf induces a longer and stronger activation of insulin receptor as demonstrated in the enhanced and prolonged Akt phosphorylation with hepatoma cells. Furthermore, ProINS-Tf can overcome insulin resistance in palmitate-treated HepG2 cells, as well as in severe hyperglycemic NOD mice. Therefore, ProINS-Tf can potentially be developed into a safe and effective insulin prodrug for the control of basal glycaemia in diabetes and for the treatment/prevention of insulin resistance- associated diseases