title: Interaction of mouse intestinal P-glycoprotein with oral antidiabetic drugs and its inhibitors.
abstract: Type 2 diabetes (T2DM) is a progressive insulin secretory defect accompanied by resistance to insulin, and thereby making glycemic control a major concern in the treatment of these patients. Oral drug administration, though a popular option for its non-invasiveness, suffer from poor bioavailability. It could be related to the efflux transport of intestinal P-glycoprotein (Pgp). In the present study, we explored the binding interactions of antidiabetic drugs i.e., sulfonylurea drugs (glimepiride, glipizide, glyburide) and rapid acting insulin secretagogues viz., nateglinide, repaglinide and rosiglitazone; and Pgp inhibitors i.e., Generation I (verapamil and tamoxifen), III (tetradrine and tariquidar), and natural inhibitors (fumagillin and piperine) in mouse Pgp model. Our results revealed that fumagillin piperine and verapamil possess maximum interaction energies with Pgp compared to antidiabetic drugs. These observations elucidate the role of fumagillin and piperine as potential natural compounds which could intervene in the efflux action of Pgp in extruding the antidiabetic drugs and may have implications for increasing efficacy of oral antidiabetic therapy.
authors.forename: Harman
authors.initials: H
authors.lastname: Kalsi
authors.forename: Ravneet K
authors.initials: RK
authors.lastname: Grewal
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology; D001693:Biological Transport, Active; D003510:Cyclohexanes / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D062105:Molecular Docking Simulation; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011485:Protein Binding; D012717:Sesquiterpenes / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids; D052117:Benzodioxoles; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D007004:Hypoglycemic Agents; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D012717:Sesquiterpenes; D013629:Tamoxifen; C026211:fumagillin; D014700:Verapamil; C008922:piperine