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Titolo:
Current therapies and emerging targets for the treatment of diabetes
Autore:
Wagman, AS; Nuss, JM;
Indirizzi:
Chiron Corp, Dept Med Chem, Small Mol Drug Discovery, Emeryville, CA 94608USA Chiron Corp Emeryville CA USA 94608 ug Discovery, Emeryville, CA 94608USA Exelixis Inc, Dept Med Chem, S San Francisco, CA 94083 USA Exelixis Inc SSan Francisco CA USA 94083 , S San Francisco, CA 94083 USA
Titolo Testata:
CURRENT PHARMACEUTICAL DESIGN
fascicolo: 6, volume: 7, anno: 2001,
pagine: 417 - 450
SICI:
1381-6128(200104)7:6<417:CTAETF>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACTIVATED RECEPTOR-GAMMA; ALDOSE REDUCTASE INHIBITOR; GLYCOGEN-SYNTHASE KINASE-3; PROTEIN-TYROSINE PHOSPHATASES; GLYCATION END-PRODUCTS; NA+-GLUCOSE COTRANSPORTER; DIPEPTIDYL-PEPTIDASE-IV; AFFINITY NA+/GLUCOSE COTRANSPORTER; SORBITOL DEHYDROGENASE INHIBITION; IMPROVES GLYCEMIC CONTROL;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
284
Recensione:
Indirizzi per estratti:
Indirizzo: Wagman, AS Chiron Corp, Dept Med Chem, Small Mol Drug Discovery, 4560 Horton St,M-S 4-5, Emeryville, CA 94608 USA Chiron Corp 4560 Horton St,M-S 4-5 Emeryville CA USA 94608 USA
Citazione:
A.S. Wagman e J.M. Nuss, "Current therapies and emerging targets for the treatment of diabetes", CUR PHARM D, 7(6), 2001, pp. 417-450

Abstract

Concurrent with the spread of the western lifestyle, the prevalence of alltypes of diabetes is on the rise in the world's population. The number of diabetics is increasing by 4-5% per year with an estimated 40-45% of individual's over the age of 65 years having either type II diabetes or impaired glucose tolerance. Since the signs of diabetes are not immediately obvious,diagnosis can be preceded by an extended period of impaired glucose tolerance resulting in the prevalence of beta-cell dysfunction and macrovascular complications. In addition to increased medical vigilance, diabetes is being combated through aggressive treatment directed at lowering circulating blood glucose and inhibiting postprandial hyperglycemic spikes. Current strategies to treat diabetes include reducing insulin resistance using glitazones, supplementing insulin supplies with exogenous insulin, increasing endogenous insulin production with sulfonylureas and meglitinides, reducing hepatic glucose production through biguanides, and limiting postprandial glucoseabsorption with alpha-glucosidase inhibitors. In all of these areas, new generations of small molecules are being investigated which exhibit improvedefficacy and safety profiles. Promising biological targets are also emerging such as (1) insulin sensitizers including protein tyrosine phosphatase-1B (PTP-1B) and glycogen synthase kinase 3 (GSK3), (2) inhibitors of gluconeogenesis like pyruvate dehydrogenase kinase (PDH) inhibitors, (3) lipolysisinhibitors, (4) fat oxidation including carnitine palmitoyltransferase (CPT) I and II inhibitors, and (5) energy expenditure by means of beta 3-adrenoceptor agonists. Also important are alternative routes of glucose disposalsuch as Na+-glucose cotransporter (SGLT) inhibitors, combination therapies, and the treatment of diabetic complications (eg. retinopathy, nephropathy, and neuropathy). With may new opportunities for drug discovery, the prospects are excellent for development of innovative therapies to effectively manage diabetes and prevent its long term complications. This review highlights recent (1997-2000) advances in diabetes therapy and research with an emphasis on small molecule drug design (275 references).

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 02:56:51