Insulin mimetics in Urtica dioica: structural and computational analyses of Urtica dioica extracts

Urtica Dioica (UD) is a plant shown to reduce blood glucose levels upon oral ingestion; however, neither its active component nor its mechanism of action has been identified. One active fraction of this extract, termed UD-1, was separated by molecular sieve column chromatography and purified by high performance liquid chromatography (HPLC). While UD-1 did not stimulate insulin secretion in glucose-responsive MIN6 clonal beta-cells, chronic exposure (24 h) significantly enhanced glucose uptake (approximately 1.5-fold) in L6-GLUT4myc myoblast cells. Using HPLC and MALDI-TOF, we further purified the UD-1 fraction into two fractions termed UD-1A and UD-1B. Computational and structural analyses strongly suggested that the antidiabetic component of UD-1 was due to one or more structurally related cyclical peptides that facilitate glucose uptake by forming unique glucose permeable pores. The structure and function of these glucose-conducting pores are discussed herein.