A genome-wide siRNA screen to identify modulators of insulin sensitivity and gluconeogenesis

PLoS ONE

Volumn 7, Issue 5, 2012, Pages

  Yang, Ruojing ^a   Lacson, Raul G ^a   Castriota, Gino ^a   Zhang, Xiaohua D ^a   Liu, Yaping ^a   Zhao, Wenqing ^a   Einstein, Monica ^a   Camargo, Luiz Miguel ^a   Qureshi, Sajjad ^a   Wong, Kenny K ^a   Zhang, Bei B ^a   Ferrer, Marc ^a   Berger, Joel P ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA LACTAMASE; CYCLIC AMP DERIVATIVE; DEXAMETHASONE; GLUCOSE; GLUCOSE 6 PHOSPHATASE; INSULIN; MESSENGER RNA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PHOSPHOENOLPYRUVATE CARBOXYLASE; PROTEIN KINASE B; PYRUVATE DEHYDROGENASE KINASE 4; SMALL INTERFERING RNA;

ARTICLE; CELL LINE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; GENE IDENTIFICATION; GENE LIBRARY; GENE SILENCING; GENE TARGETING; GENETIC SCREENING; GLUCONEOGENESIS; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; INSULIN SENSITIVITY; NON INSULIN DEPENDENT DIABETES MELLITUS; PROMOTER REGION; PROTEIN EXPRESSION; RNA INTERFERENCE; SIGNAL TRANSDUCTION; GENETIC ASSOCIATION; GENETICS; GENOMICS; HUMAN GENOME; INSULIN RESISTANCE; LIVER; METABOLISM; METHODOLOGY; TUMOR CELL LINE;

CELL LINE, TUMOR; DIABETES MELLITUS, TYPE 2; GENOME, HUMAN; GENOME-WIDE ASSOCIATION STUDY; GENOMICS; GLUCONEOGENESIS; HUMANS; INSULIN RESISTANCE; LIVER; RNA, SMALL INTERFERING;

EID: 84860741223     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0036384     Document Type: Article

References (39)

1. Saltiel AR, (2001) New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell 104: 517-529.
2. Yang R, Trevillyan JM, (2008) c-Jun N-terminal kinase pathways in diabetes. Int J Biochem Cell Biol 40: 2702-2706.
3. Zimmet P, Alberti KG, Shaw J, (2001) Global and societal implications of the diabetes epidemic. Nature 414: 782-787.
4. Hundal RS, Krssak M, Dufour S, Laurent D, Lebon V, et al. (2000) Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes 49: 2063-2069.
5. Mithieux G, Guignot L, Bordet JC, Wiernsperger N, (2002) Intrahepatic mechanisms underlying the effect of metformin in decreasing basal glucose production in rats fed a high-fat diet. Diabetes 51: 139-143.
6. Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE, (1995) Metabolic effects of metformin in non-insulin-dependent diabetes mellitus. N Engl J Med 333: 550-554.
7. Jiang G, Zhang BB, (2003) Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab 284: E671-678.
8. Brand CL, Rolin B, Jorgensen PN, Svendsen I, Kristensen JS, et al. (1994) Immunoneutralization of endogenous glucagon with monoclonal glucagon antibody normalizes hyperglycaemia in moderately streptozotocin-diabetic rats. Diabetologia 37: 985-993.
9. Liang Y, Osborne MC, Monia BP, Bhanot S, Gaarde WA, et al. (2004) Reduction in glucagon receptor expression by an antisense oligonucleotide ameliorates diabetic syndrome in db/db mice. Diabetes 53: 410-417.
10. Sloop KW, Cao JX, Siesky AM, Zhang HY, Bodenmiller DM, et al. (2004) Hepatic and glucagon-like peptide-1-mediated reversal of diabetes by glucagon receptor antisense oligonucleotide inhibitors. J Clin Invest 113: 1571-1581.
11. Johnson DG, Goebel CU, Hruby VJ, Bregman MD, Trivedi D, (1982) Hyperglycemia of diabetic rats decreased by a glucagon receptor antagonist. Science 215: 1115-1116.
12. Kim RM, Chang J, Lins AR, Brady E, Candelore MR, et al. (2008) Discovery of potent, orally active benzimidazole glucagon receptor antagonists. Bioorg Med Chem Lett 18: 3701-3705.
13. Sloop KW, Michael MD, Moyers JS, (2005) Glucagon as a target for the treatment of Type 2 diabetes. Expert Opin Ther Targets 9: 593-600.
14. Lau J, Behrens C, Sidelmann UG, Knudsen LB, Lundt B, et al. (2007) New beta-alanine derivatives are orally available glucagon receptor antagonists. J Med Chem 50: 113-128.
15. Qureshi SA, Rios Candelore M, Xie D, Yang X, Tota LM, et al. (2004) A novel glucagon receptor antagonist inhibits glucagon-mediated biological effects. Diabetes 53: 3267-3273.
16. Michael MD, Kulkarni RN, Postic C, Previs SF, Shulman GI, et al. (2000) Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell 6: 87-97.
17. Fisher SJ, Kahn CR, (2003) Insulin signaling is required for insulin's direct and indirect action on hepatic glucose production. J Clin Invest 111: 463-468.
18. Foufelle F, Ferre P, (2002) New perspectives in the regulation of hepatic glycolytic and lipogenic genes by insulin and glucose: a role for the transcription factor sterol regulatory element binding protein-1c. Biochem J 366: 377-391.
19. Accili D, Arden KC, (2004) FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell 117: 421-426.
20. Cichy SB, Uddin S, Danilkovich A, Guo S, Klippel A, et al. (1998) Protein kinase B/Akt mediates effects of insulin on hepatic insulin-like growth factor-binding protein-1 gene expression through a conserved insulin response sequence. J Biol Chem 273: 6482-6487.
21. Durham SK, Suwanichkul A, Scheimann AO, Yee D, Jackson JG, et al. (1999) FKHR binds the insulin response element in the insulin-like growth factor binding protein-1 promoter. Endocrinology 140: 3140-3146.
22. Tang ED, Nunez G, Barr FG, Guan KL, (1999) Negative regulation of the forkhead transcription factor FKHR by Akt. J Biol Chem 274: 16741-16746.
23. Guo S, Rena G, Cichy S, He X, Cohen P, et al. (1999) Phosphorylation of serine 256 by protein kinase B disrupts transactivation by FKHR and mediates effects of insulin on insulin-like growth factor-binding protein-1 promoter activity through a conserved insulin response sequence. J Biol Chem 274: 17184-17192.
24. Biggs WH, 3rd, Meisenhelder J, Hunter T, Cavenee WK, Arden KC, (1999) Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc Natl Acad Sci U S A 96: 7421-7426.
25. Nakae J, Park BC, Accili D, (1999) Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on serine 253 through a Wortmannin-sensitive pathway. J Biol Chem 274: 15982-15985.
26. Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, et al. (2001) Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413: 131-138.
27. Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, et al. (2003) Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature 423: 550-555.
28. Li X, Monks B, Ge Q, Birnbaum MJ, (2007) Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1alpha transcription coactivator. Nature 447: 1012-1016.
29. Friedman JE, Sun Y, Ishizuka T, Farrell CJ, McCormack SE, et al. (1997) Phosphoenolpyruvate carboxykinase (GTP) gene transcription and hyperglycemia are regulated by glucocorticoids in genetically obese db/db transgenic mice. J Biol Chem 272: 31475-31481.
30. Barthel A, Schmoll D, (2003) Novel concepts in insulin regulation of hepatic gluconeogenesis. Am J Physiol Endocrinol Metab 285: E685-692.
31. Huang B, Wu P, Bowker-Kinley MM, Harris RA, (2002) Regulation of pyruvate dehydrogenase kinase expression by peroxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin. Diabetes 51: 276-283.
32. Hotamisligil GS, (2006) Inflammation and metabolic disorders. Nature 444: 860-867.
33. Saad MJ, Folli F, Kahn CR, (1995) Insulin and dexamethasone regulate insulin receptors, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in Fao hepatoma cells. Endocrinology 136: 1579-1588.
34. Rondinone CM, (2006) Minireview: ribonucleic acid interference for the identification of new targets for the treatment of metabolic diseases. Endocrinology 147: 2650-2656.
35. Liang Y, Osborne MC, Monia BP, Bhanot S, Watts LM, et al. (2005) Antisense oligonucleotides targeted against glucocorticoid receptor reduce hepatic glucose production and ameliorate hyperglycemia in diabetic mice. Metabolism 54: 848-855.
36. Martel RR, Botros IW, Rounseville MP, Hinton JP, Staples RR, et al. (2002) Multiplexed screening assay for mRNA combining nuclease protection with luminescent array detection. Assay Drug Dev Technol 1: 61-71.
37. Zhang XD, (2008) Novel analytic criteria and effective plate designs for quality control in genome-scale RNAi screens. J Biomol Screen 13: 363-377.
38. Zhang XD, (2007) A new method with flexible and balanced control of false negatives and false positives for hit selection in RNA interference high-throughput screening assays. J Biomol Screen 12: 645-655.
39. Zhang XD, (2010) Assessing the size of gene or RNAi effects in multifactor high-throughput experiments. Pharmacogenomics 11: 199-213.