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.
Domola
Masoud Shabani
MS
Department of Physiology, University of Toronto, Ontario, Canada.
Vu
Vivian
V
Robson-Doucette
Christine A
CA
Sweeney
Gary
G
Wheeler
Michael B
MB
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*
D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D005947:Glucose