Akt and PTEN: β-cell mass and pancreas plasticity

Trends in Endocrinology and Metabolism

Volumn 20, Issue 5, 2009, Pages 243-251

  Elghazi, Lynda ^a   Bernal Mizrachi, Ernesto ^a,b  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF MICHIGAN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOSE; INSULIN RECEPTOR SUBSTRATE 2; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; PROTEIN KINASE B BETA;

APOPTOSIS; CELL CYCLE PROGRESSION; CELL PROLIFERATION; CELL SIZE; CELL SURVIVAL; DIABETES MELLITUS; ENZYME ACTIVATION; GENE DELETION; GLUCOSE HOMEOSTASIS; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RESISTANCE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; HUMANS; INSULIN-SECRETING CELLS; MODELS, BIOLOGICAL; PANCREAS; PROTO-ONCOGENE PROTEINS C-AKT; PTEN PHOSPHOHYDROLASE; SIGNAL TRANSDUCTION;

EID: 67649233039     PISSN: 10432760     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tem.2009.03.002     Document Type: Review

References (91)

1. Woodgett J.R. Recent advances in the protein kinase B signaling pathway. Curr. Opin. Cell Biol. 17 (2005) 150-157
2. Franke T.F. Intracellular signaling by Akt: bound to be specific. Sci. Signal. 1 (2008) e29
3. Chen W.S., et al. Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene. Genes Dev. 15 (2001) 2203-2208
4. Cho H., et al. Akt1/PKBalpha is required for normal growth but dispensable for maintenance of glucose homeostasis in mice. J. Biol. Chem. 276 (2001) 38349-38352
5. Cho H., et al. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science (New York, N.Y.) 292 (2001) 1728-1731
6. Garofalo R.S., et al. Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta. J. Clin. Invest. 112 (2003) 197-208
7. Bae S.S., et al. Isoform-specific regulation of insulin-dependent glucose uptake by Akt/protein kinase B. J. Biol. Chem. 278 (2003) 49530-49536
8. Tuttle R.L., et al. Regulation of pancreatic beta-cell growth and survival by the serine/threonine protein kinase Akt1/PKBalpha. Nat. Med. 7 (2001) 1133-1137
9. Bernal-Mizrachi E., et al. Islet beta cell expression of constitutively active Akt1/PKB alpha induces striking hypertrophy, hyperplasia, and hyperinsulinemia. J. Clin. Invest. 108 (2001) 1631-1638
10. Bernal-Mizrachi E., et al. Defective insulin secretion and increased susceptibility to experimental diabetes are induced by reduced Akt activity in pancreatic islet beta cells. J. Clin. Invest. 114 (2004) 928-936
11. Dor Y., et al. Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429 (2004) 41-46
12. Georgia S., and Bhushan A. Beta cell replication is the primary mechanism for maintaining postnatal beta cell mass. J. Clin. Invest. 114 (2004) 963-968
13. Kushner J.A., et al. Cyclins D2 and D1 are essential for postnatal pancreatic β-cell growth. Mol. Cell. Biol. 25 (2005) 3752-3762
14. Rane S.G., et al. Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in beta-islet cell hyperplasia. Nat. Genet. 22 (1999) 44-52
15. Tsutsui T., et al. Targeted disruption of CDK4 delays cell cycle entry with enhanced p27(Kip1) activity. Mol. Cell. Biol. 19 (1999) 7011-7019
16. Fatrai S., et al. Akt induces β-cell proliferation by regulating cyclin D1, cyclin D2, and p21 levels and cyclin-dependent kinase-4 activity. Diabetes 55 (2006) 318-325
17. Kitamura T., et al. The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. J. Clin. Invest. 110 (2002) 1839-1847
18. Nakamura K., et al. PDK1 regulates cell proliferation and cell cycle progression through control of cyclin D1 and p27Kip1 expression. J. Biol. Chem. 283 (2008) 17702-17711
19. Hashimoto N., et al. Ablation of PDK1 in pancreatic beta cells induces diabetes as a result of loss of beta cell mass. Nat. Genet. 38 (2006) 589-593
20. Nakae J., et al. The FoxO transcription factors and metabolic regulation. FEBS Lett. 582 (2008) 54-67
21. Okamoto H., et al. Role of the forkhead protein FoxO1 in beta cell compensation to insulin resistance. J. Clin. Invest. 116 (2006) 775-782
22. Buteau J., et al. Transcription factor FoxO1 mediates glucagon-like peptide-1 effects on pancreatic beta-cell mass. Diabetes 55 (2006) 1190-1196
23. Martinez S.C., et al. Glucose regulates Foxo1 through insulin receptor signaling in the pancreatic islet beta-cell. Diabetes 55 (2006) 1581-1591
24. Ho K.K., et al. Many forks in the path: cycling with FoxO. Oncogene 27 (2008) 2300-2311
25. Tanabe K., et al. Genetic deficiency of glycogen synthase kinase-3beta corrects diabetes in mouse models of insulin resistance. PLoS Biol. 6 (2008) 307-318
26. Liu Z., et al. Mice with beta cell overexpression of glycogen synthase kinase-3beta have reduced beta cell mass and proliferation. Diabetologia 51 (2008) 623-631
27. Mussmann R., et al. Inhibition of glycogen synthase kinase (GSK)3 promotes replication and survival of pancreatic beta cells. J. Biol. Chem. 282 (2007) 12030-12037
28. Boucher M.J., et al. Phosphorylation marks IPF1/PDX1 protein for degradation by glycogen synthase kinase 3-dependent mechanisms. J. Biol. Chem. 281 (2006) 6395-6403
29. Kida A., et al. Glycogen synthase kinase-3beta and p38 phosphorylate cyclin D2 on Thr280 to trigger its ubiquitin/proteasome-dependent degradation in hematopoietic cells. Oncogene 26 (2007) 6630-6640
30. Welters H.J., and Kulkarni R.N. Wnt signaling: relevance to beta-cell biology and diabetes. Trends Endocrinol. Metabol. TEM 19 (2008) 349-355
31. Rulifson I.C., et al. Wnt signaling regulates pancreatic beta cell proliferation. Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 6247-6252
32. Heiser P.W., et al. Stabilization of β-catenin impacts pancreas growth. Development 133 (2006) 2023-2032
33. Chu I.M., et al. The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy. Nat. Rev. Cancer 8 (2008) 253-267
34. Uchida T., et al. Deletion of Cdkn1b ameliorates hyperglycemia by maintaining compensatory hyperinsulinemia in diabetic mice. Nat. Med. 11 (2005) 175-182
35. Zhou B.P., et al. Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells. Nat. Cell Biol. 3 (2001) 245-252
36. Um S.H., et al. Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1,S6K1. Cell Metab. 3 (2006) 393-402
37. Avruch J., et al. Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase. Oncogene 25 (2006) 6361-6372
38. Sarbassov D.D., et al. Growing roles for the mTOR pathway. Curr. Opin. Cell Biol. 17 (2005) 596-603
39. Sarbassov D.D., et al. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr. Biol. 14 (2004) 1296-1302
40. Huang J., and Manning B.D. The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem. J. 412 (2008) 179-190
41. Balcazar, N. et al. mTORC1 activation regulates beta-cell mass and proliferation by modulation of cyclin D2 synthesis and stability. J. Biol. Chem. (in press)
42. Rachdi L., et al. Disruption of Tsc2 in pancreatic beta cells induces beta cell mass expansion and improved glucose tolerance in a TORC1-dependent manner. Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 9250-9255
43. Shigeyama Y., et al. Biphasic response of pancreatic beta-cell mass to ablation of tuberous sclerosis complex 2 in mice. Mol. Cell. Biol. 28 (2008) 2971-2979
44. Pende M., et al. Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice. Nature 408 (2000) 994-997
45. Leroith D., and Accili D. Mechanisms of disease: using genetically altered mice to study concepts of type 2 diabetes. Nat. Clin. Prac. 4 (2008) 164-172
46. Srinivasan S., et al. Glucose promotes pancreatic islet beta-cell survival through a PI 3-kinase/Akt-signaling pathway. Am. J. Physiol. Endocrinol. Metab. 283 (2002) E784-E793
47. Ohsugi M., et al. Reduced expression of the insulin receptor in mouse insulinoma (MIN6) cells reveals multiple roles of insulin signaling in gene expression, proliferation, insulin content, and secretion. J. Biol. Chem. 280 (2005) 4992-5003
48. Brubaker P.L., and Drucker D.J. Minireview: Glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system. Endocrinology 145 (2004) 2653-2659
49. Dickson L.M., and Rhodes C.J. Pancreatic beta-cell growth and survival in the onset of type 2 diabetes: a role for protein kinase B in the Akt?. Am. J. Physiol. Endocrinol. Metab. 287 (2004) E192-E198
50. Chen J., et al. Thioredoxin-interacting protein deficiency induces Akt/Bcl-xL signaling and pancreatic beta-cell mass and protects against diabetes. FASEB J. 22 (2008) 3581-3594
51. Kaneto H., et al. Role of oxidative stress, endoplasmic reticulum stress, and c-Jun N-terminal kinase in pancreatic beta-cell dysfunction and insulin resistance. Int. J. Biochem. Cell Biol. 37 (2005) 1595-1608
52. Eizirik D.L., et al. The role for endoplasmic reticulum stress in diabetes mellitus. Endocr. Rev. 29 (2008) 42-61
53. Du K., et al. TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver. Science (New York, N.Y.) 300 (2003) 1574-1577
54. Qian B., et al. TRIB3 is implicated in glucotoxicity- and oestrogen receptor-stress-induced beta-cell apoptosis. J. Endocrinol. 199 (2008) 407-416
55. Kang E.S., et al. O-GlcNAc modulation at Akt1 Ser473 correlates with apoptosis of murine pancreatic beta cells. Exp. Cell Res. 314 (2008) 2238-2248
56. Buteau J., and Accili D. Regulation of pancreatic beta-cell function by the forkhead protein FoxO1. Diabetes Obes. Metab. 9 Suppl 2 (2007) 140-146
57. Fu Z., and Tindall D.J. FOXOs, cancer and regulation of apoptosis. Oncogene 27 (2008) 2312-2319
58. Kim S.J., et al. Glucose-dependent insulinotropic polypeptide (GIP) stimulation of pancreatic beta-cell survival is dependent upon phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) signaling, inactivation of the forkhead transcription factor Foxo1, and down-regulation of bax expression. J. Biol. Chem. 280 (2005) 22297-22307
59. Martinez S.C., et al. Inhibition of Foxo1 protects pancreatic islet beta-cells against fatty acid and endoplasmic reticulum stress-induced apoptosis. Diabetes 57 (2008) 846-859
60. Kitamura Y.I., et al. FoxO1 protects against pancreatic beta cell failure through NeuroD and MafA induction. Cell Metab. 2 (2005) 153-163
61. Srinivasan S., et al. Endoplasmic reticulum stress-induced apoptosis is partly mediated by reduced insulin signaling through phosphatidylinositol 3-kinase/akt and increased glycogen synthase kinase-3β in mouse insulinoma cells. Diabetes 54 (2005) 968-975
62. Mishra R., et al. Glycogen synthase kinase-3beta induces neuronal cell death via direct phosphorylation of mixed lineage kinase 3. J. Biol. Chem. 282 (2007) 30393-30405
63. Grimes C.A., and Jope R.S. CREB DNA binding activity is inhibited by glycogen synthase kinase-3 beta and facilitated by lithium. J. Neurochem. 78 (2001) 1219-1232
64. Clerk A., et al. Signaling pathways mediating cardiac myocyte gene expression in physiological and stress responses. J. Cell. Physiol. 212 (2007) 311-322
65. Duronio V. The life of a cell: apoptosis regulation by the PI3K/PKB pathway. Biochem. J. 415 (2008) 333-344
66. Jhala U.S., et al. cAMP promotes pancreatic beta-cell survival via CREB-mediated induction of IRS2. Genes Dev. 17 (2003) 1575-1580
67. Emamaullee J., et al. XIAP overexpression in islet beta-cells enhances engraftment and minimizes hypoxia-reperfusion injury. Am. J. Transplant. 5 (2005) 1297-1305
68. Bouzakri K., et al. Rab GTPase-activating protein AS160 is a major downstream effector of protein kinase B/Akt signaling in pancreatic beta-cells. Diabetes 57 (2008) 1195-1204
69. Carracedo A., and Pandolfi P.P. The PTEN-PI3K pathway: of feedbacks and cross-talks. Oncogene 27 (2008) 5527-5541
70. Vivanco I., et al. Identification of the JNK signaling pathway as a functional target of the tumor suppressor PTEN. Cancer Cell 11 (2007) 555-569
71. Cully M., et al. Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat. Rev. Cancer 6 (2006) 184-192
72. Franke T.F. PI3K/Akt: getting it right matters. Oncogene 27 (2008) 6473-6488
73. Kushner J.A., et al. Phosphatase and tensin homolog regulation of islet growth and glucose homeostasis. J. Biol. Chem. 280 (2005) 39388-39393
74. Stiles B.L., et al. Selective deletion of Pten in pancreatic beta cells leads to increased islet mass and resistance to STZ-induced diabetes. Mol. Cell. Biol. 26 (2006) 2772-2781
75. Nguyen K.T., et al. Essential role of Pten in body size determination and pancreatic beta-cell homeostasis in vivo. Mol. Cell. Biol. 26 (2006) 4511-4518
76. Alliouachene S., et al. Constitutively active Akt1 expression in mouse pancreas requires S6 kinase 1 for insulinoma formation. J. Clin. Invest. 118 (2008) 3629-3638
77. Um S.H., et al. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature 431 (2004) 200-205
78. Harrington L.S., et al. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J. Cell Biol. 166 (2004) 213-223
79. Shah O.J., et al. Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies. Curr. Biol. 14 (2004) 1650-1656
80. Stanger B.Z., et al. Pten constrains centroacinar cell expansion and malignant transformation in the pancreas. Cancer Cell 8 (2005) 185-195
81. Elghazi L., et al. Regulation of pancreas plasticity and malignant transformation by Akt signaling. Gastroenterology 136 (2000) 1091-1103
82. Elghazi L., et al. Generation of a reporter mouse line expressing Akt and EGFP upon Cre-mediated recombination. Genesis 46 (2008) 256-264
83. Elghazi L., et al. Emerging role of protein kinase B/Akt signaling in pancreatic beta-cell mass and function. Int. J. Biochem. Cell Biol. 38 (2006) 157-163
84. Sarbassov D.D., et al. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science New York (N.Y.) 307 (2005) 1098-1101
85. Holst L.S., et al. Protein kinase B is expressed in pancreatic beta cells and activated upon stimulation with insulin-like growth factor I. Biochem. Biophys. Res. Commun. 250 (1998) 181-186
86. Kitamura T., and Ido Kitamura Y. Role of FoxO proteins in pancreatic beta cells. Endocr. J. 54 (2007) 507-515
87. Kops G.J., and Burgering B.M. Forkhead transcription factors: new insights into protein kinase B (c-akt) signaling. J. Mol. Med. 77 (1999) 656-665
88. Cohen P., and Frame S. The renaissance of GSK3. Nat. Rev. Mol. Cell Biol. 2 (2001) 769-776
89. Clevers H. Wnt/beta-catenin signaling in development and disease. Cell 127 (2006) 469-480
90. Yin Y., and Shen W.H. PTEN: a new guardian of the genome. Oncogene 27 (2008) 5443-5453
91. Di Cristofano A., and Pandolfi P.P. The multiple roles of PTEN in tumor suppression. Cell 100 (2000) 387-390