title: Ethylidene glucose-substituted new analogue of streptozotocin cannot induce diabetes: study on the basis of structure and activity relationship.
abstract: 4,6-O-Ethylidene glucose (ethylidene glucose), a specific inhibitor at the outer surface of a glucose transporter in the cell membranes, substituted analogue of streptozotocin was newly synthesized. This compound did not induce diabetes in rats and also did not show cytotoxic effect on pancreatic beta cells of neonatal rats in a monolayer culture system. The reasons why such a molecule was designed and why it showed no biological effects are discussed on the basis of a structure-activity relationship. Our results afford positive evidence for the presence of a glucose transport system or a glucose transporter on pancreatic beta cells and its involvement in the action of streptozotocin on beta cells.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kawada
authors.forename: M
authors.initials: M
authors.lastname: Okita
authors.forename: M
authors.initials: M
authors.lastname: Nukatsuka
authors.forename: K
authors.initials: K
authors.lastname: Toyooka
authors.forename: S
authors.initials: S
authors.lastname: Naito
authors.forename: A
authors.initials: A
authors.lastname: Nabeshima
authors.forename: K
authors.initials: K
authors.lastname: Tsujihara
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: M
authors.initials: M
authors.lastname: Nishida
mesh_terms: D000818:Animals; D001345:Autoradiography; D001786:Blood Glucose / Q000378:metabolism; D002250:Carbon Radioisotopes; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced*; D005947:Glucose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009243:NAD; C060308:4,6-ethylidene glucose streptozotocin; C013984:ethylidene glucose; D013311:Streptozocin; D005947:Glucose