ProINS-Tf

ProINS-Tf is a recombinant proinsulin–transferrin fusion protein designed as a long-acting, liver-targeted insulin prodrug for diabetes mellitus. It consists of the C-terminal portion of human proinsulin fused to the N-terminal region of human serum transferrin, exploiting the transferrin–transferrin receptor endocytic recycling pathway for targeted delivery to hepatocytes and prolonged circulation time.[1][2] After transferrin receptor–mediated endocytosis and intracellular processing, ProINS-Tf is converted to an active insulin–transferrin species (INS-Tf/irINS-Tf) that activates insulin receptors in the liver, suppresses hepatic glucose production by downregulating glucose-6-phosphatase and PEPCK, increases hepatic glycogen, and produces delayed but sustained glucose-lowering effects with reduced peripheral (muscle and adipose) insulin receptor activation.[1][2] In streptozotocin-induced diabetic mice, subcutaneous ProINS-Tf shows markedly extended plasma half-life versus proinsulin, prolonged basal glucose-lowering for up to 12–40 hours depending on regimen, and a wider safety window compared with insulin glargine by avoiding early severe hypoglycemia, supporting its development as a basal insulin replacement candidate.[1][2][5]

Other names

Proinsulin-Transferrin fusion proteinProinsulin-TfProINS-TF