Insulin hypersensitivity and resistance to streptozotocin-induced diabetes in mice lacking PTEN in adipose tissue

Molecular and Cellular Biology

Volumn 25, Issue 6, 2005, Pages 2498-2510

  Kurlawalla Martinez, Christine ^a   Stiles, Bangyan ^a   Wang, Ying ^a   Devaskar, Sherin U ^a   Kahn, Barbara B ^b   Wu, Hong ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL ENZYME; FATTY ACID; GLUCOSE; GLUCOSE TRANSPORTER 4; INSULIN; LIVER ENZYME; PHOSPHATASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN SERINE THREONINE KINASE; RESISTIN;

ADIPOSE TISSUE; ANIMAL TISSUE; ARTICLE; CELL SURFACE; CHROMOSOME 10; CONTROLLED STUDY; DRUG MECHANISM; DRUG RESISTANCE; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME REGULATION; FATTY ACID BLOOD LEVEL; GLUCOSE METABOLISM; GLUCOSE TOLERANCE; GLUCOSE TRANSPORT; INSULIN ALLERGY; INSULIN BLOOD LEVEL; INSULIN METABOLISM; INSULIN SENSITIVITY; LIPID METABOLISM; MOUSE; NONHUMAN; OBESITY; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; STREPTOZOCIN DIABETES;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ADIPOCYTES; ADIPOSE TISSUE; ANIMALS; CELL MEMBRANE; DIABETES MELLITUS, EXPERIMENTAL; FATTY ACIDS; GLUCOSE TOLERANCE TEST; GLUCOSE TRANSPORTER TYPE 4; HORMONES, ECTOPIC; INSULIN; INSULIN RESISTANCE; LIVER; MICE; MICE, KNOCKOUT; MONOSACCHARIDE TRANSPORT PROTEINS; MUSCLE CELLS; MUSCLE PROTEINS; PANCREAS; PHOSPHORIC MONOESTER HYDROLASES; PROTEIN ISOFORMS; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; PTEN PHOSPHOHYDROLASE; RESISTIN; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEINS;

ANIMALIA;

EID: 14844340146     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.25.6.2498-2510.2005     Document Type: Article

References (76)

1. Abel, E. D., O. Peroni, J. K. Kim, Y. B. Kim, O. Boss, E. Hadro, T. Minnemann, G. I. Shulman, and B. B. Kahn. 2001. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 409:729-733.
2. Accili, D., J. Drago, E. J. Lee, M. D. Johnson, M. H. Cool, P. Salvatore, L. D. Asico, P. A. Jose, S. I. Taylor, and H. Westphal. 1996. Early neonatal death in mice homozygous for a null allele of the insulin receptor gene. Nat. Genet. 12:106-109.
3. Backers, K., D. Blero, N. Paternotte, J. Zhang, and C. Erneux. 2003. The termination of PI3K signalling by SHIP1 and SHIP2 inositol 5-phosphatases. Adv. Enzyme Regul. 43:15-28.
4. Banerjee, R. R., S. M. Rangwala, J. S. Shapiro, A. S. Rich, B. Rhoades, Y. Qi, J. Wang, M. W. Rajala, A. Pocai, P. E. Scherer, C. M. Steppan, R. S. Ahima, S. Obici, L. Rossetti, and M. A. Lazar. 2004. Regulation of fasted blood glucose by resistin. Science 303:1195-1198.
5. Baudry, A., L. Leroux, M. Jackerott, and R. L. Joshi. 2002. Genetic manipulation of insulin signaling, action and secretion in mice. Insights into glucose homeostasis and pathogenesis of type 2 diabetes. EMBO Rep. 3:323-328.
6. Bluher, M., M. D. Michael, O. D. Peroni, K. Ueki, N. Carter, B. B. Kahn, and C. R. Kahn. 2002. Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance. Dev. Cell 3:25-38.
7. Brazil, D. P., and B. A. Hemmings. 2001. Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem. Sci. 26:657-664.
8. Butler, M., R. A. McKay, I. J. Popoff, W. A. Gaarde, D. Witchell, S. F. Murray, N. M. Dean, S. Bhanot, and B. P. Monia. 2002. Specific inhibition of PTEN expression reverses hyperglycemia in diabetic mice. Diabetes 51:1028-1034.
9. Cantley, L. C. 2002. The phosphoinositide 3-kinase pathway. Science 296:1655-1657.
10. Cho, H., J. Mu, J. K. Kim, J. L. Thorvaldsen, Q. Chu, E. B. Crenshaw III, K. H. Kaestner, M. S. Bartolomei, G. I. Shulman, and M. J. Birnbaum. 2001. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science 292:1728-1731.
11. Clement, S., U. Krause, F. Desmedt, J. F. Tanti, J. Behrends, X. Pesesse, T. Sasaki, J. Penninger, M. Doherty, W. Malaisse, J. E. Dumont, Y. Le Marchand-Brustel, C. Erneux, L. Hue, and S. Schurmans. 2004. The lipid phosphatase SHIP2 controls insulin sensitivity. Nature 431:878. (Erratum.)
12. Clement, S., U. Krause, F. Desmedt, J. F. Tanti, J. Behrends, X. Pesesse, T. Sasaki, J. Penninger, M. Doherty, W. Malaisse, J. E. Dumont, Y. Le Marchand-Brustel, C. Erneux, L. Hue, and S. Schurmans. 2001. The lipid phosphatase SHIP2 controls insulin sensitivity. Nature 409:92-97.
13. Cross, D. A., P. W. Watt, M. Shaw, J. van der Kaay, C. P. Downes, J. C. Holder, and P. Cohen. 1997. Insulin activates protein kinase B, inhibits glycogen synthase kinase-3 and activates glycogen synthase by rapamycin-insensitive pathways in skeletal muscle and adipose tissue. FEBS Lett. 406:211-215.
14. Elchebly, M., P. Payette, E. Michaliszyn, W. Cromlish, S. Collins, A. L. Loy, D. Normandin, A. Cheng, J. Himms-Hagen, C. C. Chan, C. Ramachandran, M. J. Gresser, M. L. Tremblay, and B. P. Kennedy. 1999. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 283:1544-1548.
15. Fasshauer, M., J. Klein, S. Neumann, M. Eszlinger, and R. Paschke. 2001. Isoproterenol inhibits resistin gene expression through a G(S)-protein-coupled pathway in 3T3-L1 adipocytes. FEBS Lett. 500:60-63.
16. Fasshauer, M., J. Klein, S. Neumann, M. Eszlinger, and R. Paschke. 2001. Tumor necrosis factor alpha is a negative regulator of resistin gene expression and secretion in 3T3-L1 adipocytes. Biochem. Biophys. Res. Commun. 288:1027-1031.
17. Fernandez-Moreno, C., J. G. Pichel, V. Chesnokova, and F. De Pablo. 2004. Increased leptin and white adipose tissue hypoplasia are sexually dimorphic in Lif null/Igf-I haploinsufficient mice. FEBS Lett. 557:64-68.
18. Fruhbeck, G., J. Gomez-Ambrosi, F. J. Muruzabal, and M. A. Burrell. 2001. The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am. J. Physiol. Endocrinol. Metab. 280:E827-E847.
19. Garofalo, R. S., S. J. Orena, K. Rafidi, A. J. Torchia, J. L. Stock, A. L. Hildebrandt, T. Coskran, S. C. Black, D. J. Brees, J. R. Wicks, J. D. McNeish, and K. G. Coleman. 2003. Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta. J. Clin. Investig. 112:197-208.
20. George, S., J. J. Rochford, C. Wolfrum, S. L. Gray, S. Schinner, J. C. Wilson, M. A. Soos, P. R. Murgatroyd, R. M. Williams, C. L. Acerini, D. B. Dunger, D. Barford, A. M. Umpleby, N. J. Wareham, H. A. Davies, A. J. Schafer, M. Stoffel, S. O'Rahilly, and I. Barroso. 2004. A family with severe insulin resistance and diabetes due to a mutation in AKT2. Science 304:1325-1328.
21. Gregoire, F. M., Q. Zhang, S. J. Smith, C. Tong, D. Ross, H. Lopez, and D. B. West. 2002. Diet-induced obesity and hepatic gene expression alterations in C57BL/6J and ICAM-1-deficient mice. Am. J. Physiol. Endocrinol. Metab. 282:E703-E113.
22. Groszer, M., R. Erickson, D. D. Scripture-Adams, R. Lesche, A. Trumpp, J. A. Zack, H. I. Kornblum, X. Liu, and H. Wu. 2001. Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo. Science 294:2186-2189.
23. Gum, R. J., L. L. Gaede, S. L. Koterski, M. Heindel, J. E. Clampit, B. A. Zinker, J. M. Trevillyan, R. G. Ulrich, M. R. Jirousek, and C. M. Rondinone. 2003. Reduction of protein tyrosine phosphatase 1B increases insulin-dependent signaling in ob/ob mice. Diabetes 52:21-28.
24. Halaas, J. L., K. S. Gajiwala, M. Maffei, S. L. Cohen, B. T. Chait, D. Rabinowitz, R. L. Lallone, S. K. Burley, and J. M. Friedman. 1995. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543-546.
25. Haugen, F., A. Jorgensen, C. A. Drevon, and P. Trayhurn. 2001. Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes. FEBS Lett. 507:105-108.
26. Hoffman, B. T., M. R. Nelson, K. Burdick, and S. M. Baxter. 2004. Protein tyrosine phosphatases: strategies for distinguishing proteins in a family containing multiple drug targets and anti-targets. Curr. Pharm. Des. 10:1161-1181.
27. Iida, S., A. Ono, K. Sayama, T. Hamaguchi, H. Fujii, H. Nakajima, M. Namba, T. Hanafusa, Y. Matsuzawa, and K. Moriwaki. 2000. Accelerated decline of blood glucose after intravenous glucose injection in a patient with Cowden disease having a heterozygous germline mutation of the PTEN/MMAC1 gene. Anticancer Res. 20:1901-1904.
28. Jiang, G., and B. B. Zhang. 2002. Pi 3-kinase and its up- and down-stream modulators as potential targets for the treatment of type II diabetes. Front. Biosci. 7:d903-d907.
29. Joshi, R. L., B. Lamothe, N. Cordonnier, K. Mesbah, E. Monthioux, J. Jami, and D. Bucchini. 1996. Targeted disruption of the insulin receptor gene in the mouse results in neonatal lethality. EMBO J. 15:1542-1547.
30. Kahn, B. B., and J. S. Flier. 2000. Obesity and insulin resistance. J. Clin. Investig. 106:473-481.
31. Kido, Y., D. J. Burks, D. Withers, J. C. Bruning, C. R. Kahn, M. F. White, and D. Accili. 2000. Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1, and IRS-2. J. Clin. Investig. 105:199-205.
32. Komazawa, N., M. Matsuda, G. Kondoh, W. Mizunoya, M. Iwaki, T. Takagi, Y. Sumikawa, K. Inoue, A. Suzuki, T. W. Mak, T. Nakano, T. Fushiki, J. Takeda, and I. Shimomura. 2004. Enhanced insulin sensitivity, energy expenditure and thermogenesis in adipose-specific Pten suppression in mice. Nat. Med. 10:1208-1215.
33. Kwon, C. H., X. Zhu, J. Zhang, L. L. Knoop, R. Tharp, R. J. Smeyne, C. G. Eberhart, P. C. Burger, and S. J. Baker. 2001. Pten regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease. Nat. Genet. 29:404-411.
34. Lesche, R., M. Groszer, J. Gao, Y. Wang, A. Messing, H. Sun, X. Liu, and H. Wu. 2002. Cre/loxP-mediated inactivation of the murine Pten tumor suppressor gene. Genesis 32:148-149.
35. Li, D. M., and H. Sun. 1997. TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor beta. Cancer Res. 57:2124-2129.
36. Like, A. A., and A. A. Rossini. 1976. Streptozotocin-induced pancreatic insulitis: new model of diabetes mellitus. Science 193:415-417.
37. Lo, Y. T., C. J. Tsao, I. M. Liu, S. S. Liou, and J. T. Cheng. 2004. Increase of PTEN gene expression in insulin resistance. Horm. Metab. Res. 36:662-666.
38. Ma, X., J. H. Warram, V. Trischitta, and A. Doria. 2002. Genetic variants at the resistin locus and risk of type 2 diabetes in Caucasians. J. Clin. Endocrinol. Metab. 87:4407-4410.
39. Maehama, T., and J. E. Dixon. 1998. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J. Biol. Chem. 273:13375-13378.
40. McTernan, C. L., P. G. McTernan, A. L. Harte, P. L. Levick, A. H. Barnett, and S. Kumar. 2002. Resistin, central obesity, and type 2 diabetes. Lancet 359:46-47.
41. Minokoshi, Y., C. R. Kahn, and B. B. Kahn. 2003. Tissue-specific ablation of the GLUT4 glucose transporter or the insulin receptor challenges assumptions about insulin action and glucose homeostasis. J. Biol. Chem. 278:33609-33612.
42. Moon, B., J. J. Kwan, N. Duddy, G. Sweeney, and N. Begum. 2003. Resistin inhibits glucose uptake in L6 cells independently of changes in insulin signaling and GLUT4 translocation. Am. J. Physiol. Endocrinol. Metab. 285:E106-E115.
43. Mosser, V. A., Y. Li, and M. J. Quon. 2001. PTEN does not modulate GLUT4 translocation in rat adipose cells under physiological conditions. Biochem. Biophys. Res. Commun. 288:1011-1017.
44. Mystkowski, P., E. Shankland, S. A. Schreyer, R. C. LeBoeuf, R. S. Schwartz, D. E. Cummings, M. Kushmerick, and M. W. Schwartz. 2000. Validation of whole-body magnetic resonance spectroscopy as a tool to assess murine body composition. Int. J. Obes. Relat. Metab. Disord. 24:719-724.
45. Nakashima, N., P. M. Sharma, T. Imamura, R. Bookstein, and J. M. Olefsky. 2000. The tumor suppressor PTEN negatively regulates insulin signaling in 3T3-L1 adipocytes. J. Biol. Chem. 275:12889-12895.
46. Nandi, A., Y. Kitamura, C. R. Kahn, and D. Accili. 2004. Mouse models of insulin resistance. Physiol. Rev. 84:623-647.
47. Neshat, M. S., I. K. Mellinghoff, C. Tran, B. Stiles, G. Thomas, R. Petersen, P. Frost, J. J. Gibbons, H. Wu, and C. L. Sawyers. 2001. Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc. Natl. Acad. Sci. USA 98:10314-10319.
48. O'Brien, B. A., B. V. Harmon, D. P. Cameron, and D. J. Allan. 1996. Beta-cell apoptosis is responsible for the development of IDDM in the multiple low-dose streptozotocin model. J. Pathol. 178:176-181.
49. Ono, H., H. Katagiri, M. Funaki, M. Anai, K. Inukai, Y. Fukushima, H. Sakoda, T. Ogihara, Y. Onishi, M. Fujishiro, M. Kikuchi, Y. Oka, and T. Asano. 2001. Regulation of phosphoinositide metabolism, Akt phosphorylation, and glucose transport by PTEN (phosphatase and tensin homolog deleted on chromosome 10) in 3T3-L1 adipocytes. Mol. Endocrinol. 15:1411-1422.
50. Pelleymounter, M. A., M. J. Cullen, M. B. Baker, R. Hecht, D. Winters, T. Boone, and F. Collins. 1995. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269:540-543.
51. Pizzuti, A., A. Argiolas, R. Di Paola, R. Baratta, A. Rauseo, M. Bozzali, R. Vigneri, B. Dallapiccola, V. Trischitta, and L. Frittitta. 2002. An ATG repeat in the 3′-untranslated region of the human resistin gene is associated with a decreased risk of insulin resistance. J. Clin. Endocrinol. Metab. 87:4403-4406.
52. Podsypanina, K., R. T. Lee, C. Politis, I. Hennessy, A. Crane, J. Puc, M. Neshat, H. Wang, L. Yang, J. Gibbons, P. Frost, V. Dreisbach, J. Blenis, Z. Gaciong, P. Fisher, C. Sawyers, L. Hedrick-Ellenson, and R. Parsons. 2001. An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice. Proc. Natl. Acad. Sci. USA 98:10320-10325.
53. Pravenec, M., L. Kazdova, V. Landa, V. Zidek, P. Mlejnek, P. Jansa, J. Wang, N. Qi, and T. W. Kurtz. 2003. Transgenic and recombinant resistin impair skeletal muscle glucose metabolism in the spontaneously hypertensive rat. J. Biol. Chem. 278:45209-45215.
54. Puigserver, P., J. Rhee, J. Donovan, C. J. Walkey, J. C. Yoon, F. Oriente, Y. Kitamura, J. Altomonte, H. Dong, D. Accili, and B. M. Spiegelman. 2003. Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature 423:550-555.
55. Satoh, H., M. T. Nguyen, P. D. Miles, T. Imamura, I. Usui, and J. M. Olefsky. 2004. Adenovirus-mediated chronic "hyper-resistinemia" leads to in vivo insulin resistance in normal rats. J. Clin. Investig. 114:224-231.
56. Shepherd, P. R., and B. B. Kahn. 1999. Glucose transporters and insulin action - implications for insulin resistance and diabetes mellitus. N. Engl. J. Med. 341:248-257.
57. Shojima, N., H. Sakoda, T. Ogihara, M. Fujishiro, H. Katagiri, M. Anai, Y. Onishi, H. Ono, K. Inukai, M. Abe, Y. Fukushima, M. Kikuchi, Y. Oka, and T. Asano. 2002. Humoral regulation of resistin expression in 3T3-L1 and mouse adipose cells. Diabetes 51:1737-1744.
58. Smith, S. R., F. Bai, C. Charbonneau, L. Janderova, and G. Argyropoulos. 2003. A promoter genotype and oxidative stress potentially link resistin to human insulin resistance. Diabetes 52:1611-1618.
59. Song, H., N. Shojima, H. Sakoda, T. Ogihara, M. Fujishiro, H. Katagiri, M. Anai, Y. Onishi, H. Ono, K. Inukai, Y. Fukushima, M. Kikuchi, H. Shimano, N. Yamada, Y. Oka, and T. Asano. 2002. Resistin is regulated by C/EBPs, PPARs, and signal-transducing molecules. Biochem. Biophys. Res. Commun. 299:291-298.
60. Stenbit, A. E., T. S. Tsao, J. Li, R. Burcelin, D. L. Geenen, S. M. Factor, K. Houseknecht, E. B. Katz, and M. J. Charron. 1997. GLUT4 heterozygous knockout mice develop muscle insulin resistance and diabetes. Nat. Med. 3:1096-1101.
61. Steppan, C. M., S. T. Bailey, S. Bhat, E. J. Brown, R. R. Banerjee, C. M. Wright, H. R. Patel, R. S. Ahima, and M. A. Lazar. 2001. The hormone resistin links obesity to diabetes. Nature 409:307-312.
62. Stiles, B., V. Gilman, N. Khanzenzon, R. Lesche, A. Li, R. Qiao, X. Liu, and H. Wu. 2002. Essential role of AKT-1/protein kinase B alpha in PTEN-controlled tumorigenesis. Mol. Cell. Biol. 22:3842-3851.
63. Stiles, B., Y. Wang, A. Stahl, S. Bassilian, W. P. Lee, Y. J. Kim, R. Sherwin, S. Devaskar, R. Lesche, M. A. Magnuson, and H. Wu. 2004. Live-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity. Proc. Natl. Acad. Sci. USA 101:2082-2087.
64. Suzuki, A., M. Hayashida, H. Kawano, K. Sugimoto, T. Nakano, and K. Shiraki. 2000. Hepatocyte growth factor promotes cell survival from fas-mediated cell death in hepatocellular carcinoma cells via Akt activation and Fas-death-inducing signaling complex suppression. Hepatology 32:796-802.
65. Suzuki, A., S. Itami, M. Ohishi, K. Hamada, T. Inoue, N. Komazawa, H. Senoo, T. Sasaki, J. Takeda, M. Manabe, T. W. Mak, and T. Nakano. 2003. Keratinocyte-specific Pten deficiency results in epidermal hyperplasia, accelerated hair follicle morphogenesis and tumor formation. Cancer Res. 63:674-681.
66. Tamemoto, H., T. Kadowaki, K. Tobe, T. Yagi, H. Sakura, T. Hayakawa, Y. Terauchi, K. Ueki, Y. Kaburagi, S. Satoh, et al. 1994. Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1. Nature 372:182-186.
67. Tan, M. S., S. Y. Chang, D. M. Chang, J. C. Tsai, and Y. J. Lee. 2003. Association of resistin gene 3′-untranslated region +62G→A polymorphism with type 2 diabetes and hypertension in a Chinese population. J. Clin. Endocrinol. Metab. 88:1258-1263.
68. Thamotharan, M., R. A. McKnight, S. Thamotharan, D. J. Kao, and S. U. Devaskar. 2003. Aberrant insulin-induced GLUT4 translocation predicts glucose intolerance in the offspring of a diabetic mother. Am. J. Physiol. Endocrinol. Metab. 284:E901-E914.
69. Tozzo, E., L. Gnudi, and B. B. Kahn. 1997. Amelioration of insulin resistance in streptozotocin diabetic mice by transgenic overexpression of GLUT4 driven by an adipose-specific promoter. Endocrinology 138:1604-1611.
70. Wang, H., W. S. Chu, C. Hemphill, and S. C. Elbein. 2002. Human resistin gene: molecular scanning and evaluation of association with insulin sensitivity and type 2 diabetes in Caucasians. J. Clin. Endocrinol. Metab. 87:2520-2524.
71. Wang, S., J. Gao, Q. Lei, N. Rozengurt, C. Pritchard, J. Jiao, G. V. Thomas, G. Li, P. Roy-Burman, P. S. Nelson, X. Liu, and H. Wu. 2003. Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell 4:209-221.
72. Way, J. M., C. Z. Gorgun, Q. Tong, K. T. Uysal, K. K. Brown, W. W. Harrington, W. R. Oliver, Jr., T. M. Willson, S. A. Kliewer, and G. S. Hotamisligil. 2001. Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor gamma agonists. J. Biol. Chem. 276:25651-25653.
73. Withers, D. J., J. S. Gutierrez, H. Towery, D. J. Burks, J. M. Ren, S. Previs, Y. Zhang, D. Bernal, S. Pons, G. I. Shulman, S. Bonner-Weir, and M. F. White. 1998. Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391:900-904.
74. Yamauchi, T., J. Kamon, Y. Minokoshi, Y. Ito, H. Waki, S. Uchida, S. Yamashita, M. Noda, S. Kita, K. Ueki, K. Eto, Y. Akanuma, P. Froguel, F. Foufelle, P. Ferre, D. Carling, S. Kimura, R. Nagai, B. B. Kahn, and T. Kadowaki. 2002. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat. Med. 8:1288-1295.
75. Yoon, J. C., P. Puigserver, G. Chen, J. Donovan, Z. Wu, J. Rhee, G. Adelmant, J. Stafford, C. R. Kahn, D. K. Granner, C. B. Newgard, and B. M. Spiegelman. 2001. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413:131-138.
76. Zhu, X., C. H. Kwon, P. W. Schlosshauer, L. H. Ellenson, and S. J. Baker. 2001. PTEN induces G(1) cell cycle arrest and decreases cyclin D3 levels in endometrial carcinoma cells. Cancer Res. 61:4569-4575.