Intervention of hepatic glucose production. Small molecule regulators of potential targets for type 2 diabetes therapy

被引：30

作者：

Barf, T ^{[1
]}

机构：

[1] Biovitrum AB, Dept Med Chem, SE-75137 Uppsala, Sweden

来源：

MINI-REVIEWS IN MEDICINAL CHEMISTRY | 2004年 / 4卷 / 08期

关键词：

glucocorticoid receptor; 11; beta-HSD1; F16BPase; glycogen phosphorylase; glucagon receptor; GSK-3; G6Pase;

D O I：

10.2174/1389557043403459

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：897 / 908

页数：12

共 90 条

[1] Selective inhibition of 11β-hydroxysteroid dehydrogenase type 1 decreases blood glucose concentrations in hyperglycaemic mice [J].

Alberts, P ;

Engblom, L ;

Edling, N ;

Forsgren, M ;

Klingström, G ;

Larsson, C ;

Rönquist-Nii, Y ;

Öhman, B ;

Abrahmsén, L .

DIABETOLOGIA, 2002, 45 (11) :1528-1532

[2]

AMOS AF, 1997, DIABETIC MED, V14, pS5

[3] Acute inhibition of glucose-6-phosphate translocator activity leads to increased de novo lipogenesis and development of hepatic steatosis without affecting VLDL production in rats [J].

Bandsma, RHJ ;

Wiegman, CH ;

Herling, AW ;

Burger, HJ ;

ter Harmsel, A ;

Meijer, AJ ;

Romijn, JA ;

Reijngoud, DJ ;

Kuipers, F .

DIABETES, 2001, 50 (11) :2591-2597

[4] Arylsulfonamidothiazoles as a new class of potential antidiabetic drugs.: Discovery of potent and selective inhibitors of the 11β-hydroxysteroid dehydrogenase type 1 [J].

Barf, T ;

Vallgårda, J ;

Emond, R ;

Häggström, C ;

Kurz, G ;

Nygren, A ;

Larwood, V ;

Mosialou, E ;

Axelsson, K ;

Olsson, R ;

Engblom, L ;

Edling, N ;

Rönquist-Nii, Y ;

Öhman, B ;

Alberts, P ;

Abrahmsén, L .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (18) :3813-3815

[5] Molecular mode of inhibition of glycogenolysis in rat liver by the dihydropyridine derivative, BAY R3401 - Inhibition and inactivation of glycogen phosphorylase by an activated metabolite [J].

Bergans, N ;

Stalmans, W ;

Goldmann, S ;

Vanstapel, F .

DIABETES, 2000, 49 (09) :1419-1426

[6]

Boyle PJ, 1993, DIABETES REV, V1, P301

[7]

BRAND CL, 1996, DIABETES S1, V45, pA143

[8] Characterization of a novel, non-peptidyl antagonist of the human glucagon receptor [J].

Cascieri, MA ;

Koch, GE ;

Ber, E ;

Sadowski, SJ ;

Louizides, D ;

de Laszlo, SE ;

Hacker, C ;

Hagmann, WK ;

MacCoss, M ;

Chicchi, GG ;

Vicario, PP .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (13) :8694-8697

[9] Effects of a novel glycogen synthase kinase-3 inhibitor on insulin-stimulated glucose metabolism in Zucker diabetic fatty (falfa) rats [J].

Cline, GW ;

Johnson, K ;

Regittnig, W ;

Perret, P ;

Tozzo, E ;

Xiao, L ;

Damico, C ;

Shulman, GI .

DIABETES, 2002, 51 (10) :2903-2910

[10] Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription [J].

Coghlan, MP ;

Culbert, AA ;

Cross, DAE ;

Corcoran, SL ;

Yates, JW ;

Pearce, NJ ;

Rausch, OL ;

Murphy, GJ ;

Carter, PS ;

Cox, LR ;

Mills, D ;

Brown, MJ ;

Haigh, D ;

Ward, RW ;

Smith, DG ;

Murray, KJ ;

Reith, AD ;

Holder, JC .

CHEMISTRY & BIOLOGY, 2000, 7 (10) :793-803

← 1 2 3 4 5 6 7 8 9 →