title: Insulin mimetics in Urtica dioica: structural and computational analyses of Urtica dioica extracts.
abstract: 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.
authors.affiliation: Department of Physiology, University of Toronto, Ontario, Canada.
authors.forename: Masoud Shabani
authors.initials: MS
authors.lastname: Domola
authors.forename: Vivian
authors.initials: V
authors.lastname: Vu
authors.forename: Christine A
authors.initials: CA
authors.lastname: Robson-Doucette
authors.forename: Gary
authors.initials: G
authors.lastname: Sweeney
authors.forename: Michael B
authors.initials: MB
authors.lastname: Wheeler
mesh_terms: D000818:Animals; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008958:Models, Molecular; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D026982:Urtica dioica / Q000737:chemistry*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D005947:Glucose