title: Selective PPAR agonists for the treatment of type 2 diabetes.
abstract: Type 2 diabetes is a metabolic disease characterized by increased plasma glucose and insulin as well as dyslipidemia. If left untreated, chronic diseases will develop that are associated with neuropathic damage and higher mortality risk. Using a rational drug design, novel compounds have been developed that selectively activate the human PPAR receptors, leading to lessening of hyperglycemia and hyperinsulinemia as well as reduction of lipid levels in conjunction with an increase of the beneficial HDL-cholesterol. These PPAR agonists showed increased potency and efficacy compared to previously marketed insulin sensitizers. Lead compounds with desirable pharmacokinetic properties were chosen for further testing in several animal models. The in vivo activity of some synthetic ligands, capable of activating two or all three members of peroxisome proliferator-activated receptors (PPAR) family of receptors, suggested that they may have improved efficacy in type 2 diabetes therapy. Here, we briefly summarize the development of some novel PPAR agonists identified by our group in recent years.
authors.affiliation: Novo Nordisk A/S, Måløv, Denmark. jan.nehlin@ouh.fyns-amt.dk
authors.forename: Jan O
authors.initials: JO
authors.lastname: Nehlin
authors.forename: John P
authors.initials: JP
authors.lastname: Mogensen
authors.forename: Ingrid
authors.initials: I
authors.lastname: Petterson
authors.forename: Lone
authors.initials: L
authors.lastname: Jeppesen
authors.forename: Jan
authors.initials: J
authors.lastname: Fleckner
authors.forename: Erik M
authors.initials: EM
authors.lastname: Wulff
authors.forename: Per
authors.initials: P
authors.lastname: Sauerberg
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D050171:Dyslipidemias / Q000188:drug therapy; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D008954:Models, Biological; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000145:classification / Q000502:physiology
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D047492:Peroxisome Proliferator-Activated Receptors