title: Prospects for pharmacologic inhibition of hepatic glucose production.
abstract: Type 2 diabetes is a widespread disease where effective pharmacologic therapies can have a profound beneficial public health impact. Increased hepatic glucose production (HGP) is observed in diabetics and its moderation by currently available agents provides therapeutic benefits. This review describes the challenges associated with the discovery of small molecules that inhibit HGP. Gluconeogenesis, glycogenolysis, liver architecture, and hepatocyte composition are described to provide background information on hepatic function. Current methods of target validation for drug discovery, HGP measurement, diabetes animal models, as well as current drug therapies are covered. In the accompanying review article the new drug targets being probed to produce the next generation of therapies are described. Significant pharmaceutical and academic efforts to pharmacologically inhibit HGP has the opportunity to provide new therapeutics for type 2 diabetics.
authors.affiliation: Metabolic Disease Research, Abbott Laboratories, 100 Abbott Park Road, Abbott, Park, IL 60064-6098, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kurukulasuriya
authors.forename: J T
authors.initials: JT
authors.lastname: Link
authors.forename: D J
authors.initials: DJ
authors.lastname: Madar
authors.forename: Z
authors.initials: Z
authors.lastname: Pei
authors.forename: J J
authors.initials: JJ
authors.lastname: Rohde
authors.forename: S J
authors.initials: SJ
authors.lastname: Richards
authors.forename: A J
authors.initials: AJ
authors.lastname: Souers
authors.forename: B G
authors.initials: BG
authors.lastname: Szczepankiewicz
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004764:Enterohepatic Circulation / Q000187:drug effects; D005947:Glucose / Q000096:biosynthesis*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000819:agonists / Q000037:antagonists & inhibitors
chemical_list: D002352:Carrier Proteins; D007004:Hypoglycemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D005947:Glucose