title: An AlphaScreen Assay for the Discovery of Synthetic Chemical Inhibitors of Glucagon Production.
abstract: Glucose homeostasis is primarily controlled by two opposing hormones, insulin and glucagon, and diabetes results when insulin fails to inhibit glucagon action. Recent efforts to control glucagon in diabetes have focused on antagonizing the glucagon receptor, which is effective in lowering blood glucose levels but leads to hyperglucogonemia in rodents. An alternative strategy would be to control glucagon production with small molecules. In pursuit of this goal, we developed a homogeneous AlphaScreen assay for measuring glucagon in cell culture media and used this in a high-throughput screen to discover synthetic compounds that inhibited glucagon secretion from an alpha cell-like cell line. Some of these compounds inhibited transcription of the glucagon gene.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Evans
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Posner
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Medical Service, Veteran's Administration North Texas Health Care System, Dallas, TX, USA.
authors.forename: Roger H
authors.initials: RH
authors.lastname: Unger
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA michael.roth@utsouthwestern.edu.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Roth
mesh_terms: D000818:Animals; D001710:Biotin / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D015870:Gene Expression; D017930:Genes, Reporter; D005934:Glucagon / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D050416:Glucagon-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D057166:High-Throughput Screening Assays; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D008156:Luciferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D019809:Streptavidin / Q000737:chemistry
chemical_list: D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D054852:Small Molecule Libraries; D001710:Biotin; D005934:Glucagon; D019809:Streptavidin; D008156:Luciferases
keywords: AlphaScreen; competition assay; diabetes; glucagon