Intervention of hepatic glucose production. Small molecule regulators of potential targets for Type 2 diabetes therapy.
Excessive hepatic glucose production is thought to be a major contributor to the type 2 diabetic state. Drug discovery efforts have yielded small synthetic inhibitors for gluconeogenic and glycogenic regulators of this pathway. The most advanced targets are outlined in this mini-review and include: the glucocorticoid receptor, 11 beta-hydroxysteroid dehydrogenase type 1, fructose 1,6-bisphosphatase, the glucagon receptor, glycogen phosphorylase, glycogen synthase kinase-3, and glucose-6-phosphatase.
Barf
Tjeerd
T
Department of Medicinal Chemistry, Biovitrum AB, Box 6443, SE-751 37 Uppsala, Sweden. Tjeerd.Barf@biovitrum.com
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004798:Enzymes / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D008968:Molecular Conformation; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors
D004798:Enzymes; D007004:Hypoglycemic Agents; D018027:Receptors, Glucagon; D011965:Receptors, Glucocorticoid; D006003:Glycogen; D005947:Glucose