Pancreatic b-Cell failure mediated by mTORC1 hyperactivity and autophagic impairment

Diabetes

Volumn 63, Issue 9, 2014, Pages 2996-3008

  Bartolomé, Alberto ^a,b,c   Kimura Koyanagi, Maki ^d   Asahara, Shun Ichiro ^d   Guillén, Carlos ^b,c   Inoue, Hiroyuki ^a   Teruyama, Kyoko ^a   Shimizu, Shinobu ^a   Kanno, Ayumi ^d   García Aguilar, Ana ^b,c   Koike, Masato ^e   Uchiyama, Yasuo ^e   Benito, Manuel ^b,c   Noda, Tetsuo ^f   Kido, Yoshiaki ^a,d  

^a KOBE UNIVERSITY   (Japan)

^b UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^c INSTITUTO DE SALUD CARLOS III   (Spain)

^d KOBE UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^e JUNTENDO UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^f CANCER INSTITUTE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; HEAT SHOCK PROTEIN; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; SIGNAL TRANSDUCING ADAPTOR PROTEIN; SQSTM1 PROTEIN, MOUSE; TARGET OF RAPAMYCIN KINASE; TUBERIN; TUMOR SUPPRESSOR PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; ARTICLE; AUTOPHAGY; CONTROLLED STUDY; ENDOPLASMIC RETICULUM STRESS; GENE; HYPERGLYCEMIA; INSULIN RESISTANCE; MITOPHAGY; MOUSE; NONHUMAN; PANCREAS ISLET BETA CELL; PHENOTYPE; PRIORITY JOURNAL; TSC2 GENE; ANIMAL; HEK293 CELL LINE; HUMAN; MALE; METABOLISM; PATHOLOGY; PHYSIOLOGY;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; APOPTOSIS; AUTOPHAGY; ENDOPLASMIC RETICULUM STRESS; HEAT-SHOCK PROTEINS; HEK293 CELLS; HUMANS; INSULIN RESISTANCE; INSULIN-SECRETING CELLS; MALE; MICE; MULTIPROTEIN COMPLEXES; TOR SERINE-THREONINE KINASES; TUMOR SUPPRESSOR PROTEINS;

EID: 84906672871     PISSN: 00121797     EISSN: 1939327X     Source Type: Journal    
DOI: 10.2337/db13-0970     Document Type: Article

References (52)

1. Um SH, Frigerio F, Watanabe M, et al. Absence of S6K1 protects against ageand diet-induced obesity while enhancing insulin sensitivity. Nature 2004;431:200-205
2. Tremblay F, Brûlé S, Hee Um S, et al. Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance. Proc Natl Acad Sci U S A 2007;104:14056-14061
3. Shigeyama Y, Kobayashi T, Kido Y, et al. Biphasic response of pancreatic beta-cell mass to ablation of tuberous sclerosis complex 2 in mice. Mol Cell Biol 2008;28:2971-2979
4. Rachdi L, Balcazar N, Osorio-Duque F, 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 2008;105:9250-9255
5. Hamada S, Hara K, Hamada T, et al. Upregulation of the mammalian target of rapamycin complex 1 pathway by Ras homolog enriched in brain in pancreatic beta-cells leads to increased beta-cell mass and prevention of hyperglycemia. Diabetes 2009;58:1321-1332
6. Xie J, Herbert TP. The role of mammalian target of rapamycin (mTOR) in the regulation of pancreatic b-cell mass: implications in the development of type-2 diabetes. Cell Mol Life Sci 2012;69:1289-1304
7. Fraenkel M, Ketzinel-Gilad M, Ariav Y, et al. mTOR inhibition by rapamycin prevents beta-cell adaptation to hyperglycemia and exacerbates the metabolic state in type 2 diabetes. Diabetes 2008;57:945-957
8. Zahr E, Molano RD, Pileggi A, et al. Rapamycin impairs in vivo proliferation of islet beta-cells. Transplantation 2007;84:1576-1583
9. Ozcan U, Ozcan L, Yilmaz E, et al. Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded protein response to regulate insulin signaling and apoptosis. Mol Cell 2008;29:541-551
10. Matsuda T, Kido Y, Asahara S-I, et al. Ablation of C/EBPbeta alleviates ER stress and pancreatic beta cell failure through the GRP78 chaperone in mice. J Clin Invest 2010;120:115-126
11. Ueki K, Okada T, Hu J, et al. Total insulin and IGF-I resistance in pancreatic beta cells causes overt diabetes. Nat Genet 2006;38:583-588
12. Koyanagi M, Asahara S-I, Matsuda T, et al. Ablation of TSC2 enhances insulin secretion by increasing the number of mitochondria through activation of mTORC1. PLoS One 2011;6:e23238
13. Ebato C, Uchida T, Arakawa M, et al. Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. Cell Metab 2008;8:325-332
14. Jung HS, Chung KW, Won Kim J, et al. Loss of autophagy diminishes pancreatic beta cell mass and function with resultant hyperglycemia. Cell Metab 2008;8:318-324
15. Ogata M, Hino S-I, Saito A, et al. Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol 2006;26:9220-9231
16. Bartolomé A, Guillén C, Benito M. Autophagy plays a protective role in endoplasmic reticulum stress-mediated pancreatic β cell death. Autophagy 2012;8:1757-1768
17. Quan W, Hur KY, Lim Y, et al. Autophagy deficiency in beta cells leads to compromised unfolded protein response and progression from obesity to diabetes in mice. Diabetologia 2012;55:392-403
18. Noda T, Ohsumi Y. Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem 1998;273:3963-3966
19. Ng S, Wu Y-T, Chen B, Zhou J, Shen H-M. Impaired autophagy due to constitutive mTOR activation sensitizes TSC2-null cells to cell death under stress. Autophagy 2011;7:1173-1186
20. Parkhitko A, Myachina F, Morrison TA, et al. Tumorigenesis in tuberous sclerosis complex is autophagy and p62/sequestosome 1 (SQSTM1)-dependent. Proc Natl Acad Sci U S A 2011;108:12455-12460
21. Tudurí E, Filiputti E, Carneiro EM, Quesada I. Inhibition of Ca2+ signaling and glucagon secretion in mouse pancreatic alpha-cells by extracellular ATP and purinergic receptors. Am J Physiol Endocrinol Metab 2008;294:E952-E960
22. Kawamori D, Kurpad AJ, Hu J, et al. Insulin signaling in alpha cells modulates glucagon secretion in vivo. Cell Metab 2009;9:350-361
23. Bartolomé A, Guillén C, Benito M. Role of the TSC1-TSC2 complex in the integration of insulin and glucose signaling involved in pancreatic beta-cell proliferation. Endocrinology 2010;151:3084-3094
24. Huang J, Dibble CC, Matsuzaki M, Manning BD. The TSC1-TSC2 complex is required for proper activation of mTOR complex 2. Mol Cell Biol 2008;28:4104-4115
25. Nakae J, Biggs WH 3rd, Kitamura T, et al. Regulation of insulin action and pancreatic beta-cell function by mutated alleles of the gene encoding forkhead transcription factor Foxo1. Nat Genet 2002;32:245-253
26. Huang C-J, Haataja L, Gurlo T, et al. Induction of endoplasmic reticulum stress-induced beta-cell apoptosis and accumulation of polyubiquitinated proteins by human islet amyloid polypeptide. Am J Physiol Endocrinol Metab 2007; 293:E1656-E1662
27. Pankiv S, Clausen TH, Lamark T, et al. p62/SQSTM1 binds directly to Atg8/ LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 2007;282:24131-24145
28. Pende M, Kozma SC, Jaquet M, et al. Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice. Nature 2000; 408:994-997
29. Elghazi L, Balcazar N, Blandino-Rosano M, et al. Decreased IRS signaling impairs beta-cell cycle progression and survival in transgenic mice overexpressing S6K in beta-cells. Diabetes 2010;59:2390-2399
30. Castets P, Lin S, Rion N, et al. Sustained activation of mTORC1 in skeletal muscle inhibits constitutive and starvation-induced autophagy and causes a severe, late-onset myopathy. Cell Metab 2013;17:731-744
31. Sengupta S, Peterson TR, Laplante M, Oh S, Sabatini DM. mTORC1 controls fasting-induced ketogenesis and its modulation by ageing. Nature 2010;468: 1100-1104
32. Harrison DE, Strong R, Sharp ZD, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 2009;460:392-395
33. Selman C, Tullet JMA, Wieser D, et al. Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 2009;326:140-144
34. Stoffers DA, Ferrer J, Clarke WL, Habener JF. Early-onset type-II diabetes mellitus (MODY4) linked to IPF1. Nat Genet 1997;17:138-139
35. Martinez SC, Tanabe K, Cras-Méneur C, Abumrad NA, Bernal-Mizrachi E, Permutt MA. Inhibition of Foxo1 protects pancreatic islet beta-cells against fatty acid and endoplasmic reticulum stress-induced apoptosis. Diabetes 2008;57:846-859
36. Sachdeva MM, Claiborn KC, Khoo C, et al. Pdx1 (MODY4) regulates pancreatic beta cell susceptibility to ER stress. Proc Natl Acad Sci U S A 2009;106:19090-19095
37. Oyadomari S, Koizumi A, Takeda K, et al. Targeted disruption of the Chop gene delays endoplasmic reticulum stress-mediated diabetes. J Clin Invest 2002; 109:525-532
38. Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P. mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature 2007;450:736-740
39. Narendra D, Kane LA, Hauser DN, Fearnley IM, Youle RJ. p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy 2010;6:1090-1106
40. Okatsu K, Saisho K, Shimanuki M, et al. p62/SQSTM1 cooperates with Parkin for perinuclear clustering of depolarized mitochondria. Genes Cells 2010;15:887-900
41. Ganley IG, Lam H, Wang J, Ding X, Chen S, Jiang X. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem 2009;284:12297-12305
42. Kim J, Kundu M, Viollet B, Guan K-L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2011;13:132-141
43. Egan DF, Shackelford DB, Mihaylova MM, et al. Phosphorylation of ULK1 (hATG1) by AMP-Activated protein kinase connects energy sensing to mitophagy. Science 2011;331:456-461
44. Westermann B. Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol 2010;11:872-884
45. Molina AJA, Wikstrom JD, Stiles L, et al. Mitochondrial networking protects beta-cells from nutrient-induced apoptosis. Diabetes 2009;58:2303-2315
46. Chen H, Chomyn A, Chan DC. Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem 2005;280:26185-26192
47. Gilkerson RW, De Vries RLA, Lebot P, et al. Mitochondrial autophagy in cells with mtDNA mutations results from synergistic loss of transmembrane potential and mTORC1 inhibition. Hum Mol Genet 2012;21:978-990
48. Twig G, Elorza A, Molina AJA, et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 2008;27:433-446
49. Wu JJ, Quijano C, Chen E, et al. Mitochondrial dysfunction and oxidative stress mediate the physiological impairment induced by the disruption of autophagy. Aging (Albany, NY Online) 2009;1:425-437
50. Lu H, Koshkin V, Allister EM, Gyulkhandanyan AV, Wheeler MB. Molecular and metabolic evidence for mitochondrial defects associated with beta-cell dysfunction in a mouse model of type 2 diabetes. Diabetes 2010;59:448-459
51. Cheng Z, Guo S, Copps K, et al. Foxo1 integrates insulin signaling with mitochondrial function in the liver. Nat Med 2009;15:1307-1311
52. Barlow AD, Xie J, Moore CE, et al. Rapamycin toxicity in MIN6 cells and rat and human islets is mediated by the inhibition of mTOR complex 2 (mTORC2). Diabetologia 2012;55:1355-1365