Clozapine impairs insulin action by up-regulating Akt phosphorylation and Ped/Pea-15 protein abundance

Journal of Cellular Physiology

Volumn 227, Issue 4, 2012, Pages 1485-1492

  Panariello, Fabio ^a   Perruolo, Giuseppe ^a   Cassese, Angela ^a   Giacco, Ferdinando ^a   Botta, Ginevra ^a   Barbagallo, Alessia P M ^a   Muscettola, Giovanni ^a   Beguinot, Francesco ^a   Formisano, Pietro ^a   de Bartolomeis, Andrea ^a  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CLOZAPINE; INSULIN; INSULIN RECEPTOR; PEA 15 PROTEIN; PROTEIN; PROTEIN KINASE B; PROTEIN KINASE C ZETA; TYROSINE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CAUDATE NUCLEUS; CELL POPULATION; CONTROLLED STUDY; ENZYME PHOSPHORYLATION; GLUCOSE METABOLISM; GLUCOSE TRANSPORT; IMMUNOPRECIPITATION; IN VITRO STUDY; IN VIVO STUDY; INSULIN RESISTANCE; INSULIN RESPONSE; MALE; MOUSE; NERVE CELL; NONHUMAN; PHEOCHROMOCYTOMA CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PUTAMEN; RAT; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; TREATMENT DURATION; WESTERN BLOTTING;

ANIMALS; ANTIPSYCHOTIC AGENTS; CELL LINE; CLOZAPINE; GLUCOSE; INSULIN; INSULIN RECEPTOR SUBSTRATE PROTEINS; INSULIN RESISTANCE; MALE; MICE; MICE, INBRED C57BL; MUSCLE FIBERS, SKELETAL; NEURONS; PC12 CELLS; PHOSPHOPROTEINS; PHOSPHORYLATION; PROTEIN KINASE C; PROTO-ONCOGENE PROTEINS C-AKT; RATS; RECEPTOR, INSULIN; SIGNAL TRANSDUCTION; UP-REGULATION;

MUS;

EID: 84855748927     PISSN: 00219541     EISSN: 10974652     Source Type: Journal    
DOI: 10.1002/jcp.22864     Document Type: Article

References (66)

1. Adams PF, Marano MA. 1995. Current estimates from the National Health Interview Survey, 1994. Vital Health Stat 10:1-260.
2. Ader M, Kim SP, Catalano KJ, Ionut V, Hucking K, Richey JM, Kabir M, Bergman RN. 2005. Metabolic dysregulation with atypical antipsychotics occurs in the absence of underlying disease: A placebo-controlled study of olanzapine and risperidone in dogs. Diabetes 54:862-871.
3. Araujo H, Danziger N, Cordier J, Glowinski J, Chneiweiss H. 1993. Characterization of PEA-15, a major substrate for protein kinase C in astrocytes. J Biol Chem 268:5911-5920.
4. Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG. 2005. An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell 122:261-273.
5. Bertacca A, Ciccarone A, Cecchetti P, Vianello B, Laurenza I, Maffei M, Chiellini C, Del Prato S, Benzi L. 2005. Continually high insulin levels impair Akt phosphorylation and glucose transport in human myoblasts. Metabolism 54:1687-1693.
6. Brazil DP, Yang ZZ, Hemmings BA. 2004. Advances in protein kinase B signalling: AKTion on multiple fronts. Trends Biochem Sci 29:233-242.
7. Brown S. 1997. Excess mortality of schizophrenia. A meta-analysis. Br J Psychiatry 171:502-508.
8. Brozinick JT, Jr., Roberts BR, Dohm GL. 2003. Defective signaling through Akt-2 and -3 but not Akt-1 in insulin-resistant human skeletal muscle: Potential role in insulin resistance. Diabetes 52:935-941.
9. Chakraborty C. 2006. Biochemical and molecular basis of insulin resistance. Curr Protein Pept Sci 7:113-121.
10. Cheng CY, Hong CJ, Tsai SJ. 2005. Effects of subchronic clozapine administration on serum glucose, cholesterol and triglyceride levels, and body weight in male BALB/c mice. Life Sci 76:2269-2273.
11. Citrome L, Volavka J. 2004. Consensus development conference on antipsychotic drugs and obesity and diabetes: Response to consensus statement. Diabetes Care 27:2087-2088.
12. Citrome L, Blonde L, Damatarca C. 2005. Metabolic issues in patients with severe mental illness. South Med J 98:714-720.
13. Citrome LL, Holt RI, Zachry WM, Clewell JD, Orth PA, Karagianis JL, Hoffmann VP. 2007. Risk of treatment-emergent diabetes mellitus in patients receiving antipsychotics. Ann Pharmacother 41:1593-1603.
14. Condorelli G, Vigliotta G, Iavarone C, Caruso M, Tocchetti CG, Andreozzi F, Cafieri A, Tecce MF, Formisano P, Beguinot L, Beguinot F. 1998. PED/PEA-15 gene controls glucose transport and is overexpressed in type 2 diabetes mellitus. EMBO J 17:3858-3866.
15. Condorelli G, Vigliotta G, Trencia A, Maitan MA, Caruso M, Miele C, Oriente F, Santopietro S, Formisano P, Beguinot F. 2001. Protein kinase C (PKC)-alpha activation inhibits PKC-zeta and mediates the action of PED/PEA-15 on glucose transport in the L6 skeletal muscle cells. Diabetes 50:1244-1252.
16. Dikic I, Schlessinger J, Lax I. 1994. PC12 cells overexpressing the insulin receptor undergo insulin-dependent neuronal differentiation. Curr Biol 4:702-708.
17. Duarte AI, Santos P, Oliveira CR, Santos MS, Rego AC. 2008. Insulin neuroprotection against oxidative stress is mediated by Akt and GSK-3beta signaling pathways and changes in protein expression. Biochim Biophys Acta 1783:994-1002.
18. Dwyer DS, Pinkofsky HB, Liu Y, Bradley RJ. 1999. Antipsychotic drugs affect glucose uptake and the expression of glucose transporters in PC12 cells. Biol Psychiatry 23:69-80.
19. Dynes JB. 1969. Mental health-cause of death in schizophrenia. Va Med Mon 96:3340.
20. Eckert A, Böck BC, Tagscherer KE, Haas TL, Grund K, Sykora J, Herold-Mende C, Ehemann V, Hollstein M, Chneiweiss H, Wiestler OD, Walczak H, Roth W. 2008. The PEA-15/PED protein protects glioblastoma cells from glucose deprivation-induced apoptosis via the ERK/MAP kinase pathway. Oncogene 27:1155-1166.
21. Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA. 2004. Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat Genet 36:131-137.
22. Esposito I, Proto MC, Gazzerro P, Laezza C, Miele C, Alberobello AT, D'Esposito V, Beguinot F, Formisano P, Bifulco M. 2008. The cannabinoid CB1 receptor antagonist rimonabant stimulates 2-deoxyglucose uptake in skeletal muscle cells by regulating the expression of phosphatidylinositol-3-kinase. Mol Pharmacol 74:1678-1686.
23. Felker B, Yazel JJ, Short D. 1996. Mortality and medical comorbidity among psychiatric patients: A review. Psychiatr Serv 47:1356-1363.
24. Fiory F, Oriente F, Miele C, Romano C, Trencia A, Alberobello AT, Esposito I, Valentino R, Beguinot F, Formisano P. 2004. Protein kinase C-zeta and protein kinase B regulate distinct steps of insulin endocytosis and intracellular sorting. J Biol Chem 279:11137-11145.
25. Fiory F, Formisano P, Perruolo G, Beguinot F. 2009. Frontiers: PED/PEA-15, a multifunctional protein controlling cell survival and glucose metabolism. Am J Physiol Endocrinol Metab 297:E592-E601.
26. Girault JA, Greengard P. 2004. The neurobiology of dopamine signaling. Arch Neurol 61:641-644. Erratum in: Arch Neurol. 61: 1180.
27. Grillo CA, Piroli GG, Hendry RM, Reagan LP. 2009. Insulin-stimulated translocation of GLUT4 to the plasma membrane in rat hippocampus is PI3-kinase dependent. Brain Res 1296:35-45.
28. Haupt DW, Kane JM. 2007. Metabolic risks and effects of atypical antipsychotic treatment. J Clin Psychiatry 68:e24.
29. Hou JC, Pessin JE. 2007. Ins (endocytosis) and outs (exocytosis) of GLUT4 trafficking. Curr Opin Cell Biol 19:466-473.
30. Howes OD, Bhatnagar A, Gaughran FP, Amiel SA, Murray RM, Pilowsky LS. 2004. A prospective study of impairment in glucose control caused by clozapine without changes in insulin resistance. Am J Psychiatry 161:361-363.
31. Jin H, Meyer JM, Jeste DV. 2004. Atypical antipsychotics and glucose dysregulation: A systematic review. Schizophr Res 71:195-212.
32. Kang UG, Seo MS, Roh MS, Kim Y, Yoon SC, Kim YS. 2004. The effects of clozapine on the GSK-3-mediated signaling pathway. FEBS Lett 560:115-119.
33. Kaur G, Kulkarni SK. 2002. Studies on modulation of feeding behavior by atypical antipsychotics in female mice. Prog Neuropsychopharmacol Biol Psychiatry 26:277-285.
34. Koller EA, Doraiswamy PM. 2002. Olanzapine-associated diabetes mellitus. Pharmacotherapy 22:841-852.
35. Koller E, Schneider B, Bennett K, Dubitsky G. 2001. Clozapine-associated diabetes. Am J Med 111:716-723.
36. Lamberti JS, Crilly JF, Maharaj K, Olson D, Wiener K, Dvorin S, et al. 2004. Prevalence of diabetes mellitus among outpatients with severe mental disorders receiving atypical antipsychotic drugs. J Clin Psychiatry 65:702-706.
37. Lean ME, Pajonk FG. 2003. Patients on atypical antipsychotic drugs: Another high-risk group for type 2 diabetes. Diabetes Care 26:1597-1605.
38. Lebovitz HE. 2003. Metabolic consequences of atypical antipsychotic drugs. Psychiatr Q 74:277-290.
39. Leney SE, Tavaré JM. 2009. The molecular basis of insulin-stimulated glucose uptake: Signalling, trafficking and potential drug targets. J Endocrinol 203:1-18.
40. Lovestone S, Killick R, Di Forti M, Murray R. 2007. Schizophrenia as a GSK-3 dysregulation disorder. Trends Neurosci 30:142-149.
41. Lu XH, Dwyer DS. 2005. Second-generation antipsychotic drugs, olanzapine, quetiapine, and clozapine enhance neurite outgrowth in PC12 cells via PI3K/AKT, ERK, and pertussis toxin-sensitive pathways. J Mol Neurosci 27:43-64.
42. Mackin P, Watkinson HM, Young AH. 2005. Prevalence of obesity, glucose homeostasis disorders and metabolic syndrome in psychiatric patients taking typical or atypical antipsychotic drugs: A crosssectional study. Diabetologia 48:215-221.
43. Mueser KT, McGurk SR. 2004. Schizophrenia. Lancet 363:2063-2072.
44. Mukherjee S, Schnur DB, Reddy R. 1989. Family history of type 2 diabetes in schizophrenic patients. Lancet 8636:495.
45. Mukherjee S, Decina P, Bocola V, Saraceni F, Scapicchio PL. 1996. Diabetes mellitus in schizophrenic patients. Compr Psychiatry 37:68-73.
46. Newcomer JW. 2004. Metabolic risk during antipsychotic treatment. Clin Ther 26:1936-1946.
47. Newman SC, Bland RC. 1991. Mortality in a cohort of patients with schizophrenia: A record linkage study. Can J Psychiatry 36:239-245.
48. Nikam SS, Awasthi AK. 2008. Evolution of schizophrenia drugs: A focus on dopaminergic systems. Curr Opin Investig Drugs 9:37-46.
49. Paxinos G, Watson C. 1997. The rat brain stereotaxic coordinates. New York: Academic Press.
50. Perez-Iglesias R, Crespo-Facorro B, Amado JA, Garcia-Unzueta MT, Ramirez-Bonilla ML, Gonzalez-Blanch C, Martinez-Garcia O, Vazquez-Barquero JL. 2007. A 12-week randomized clinical trial to evaluate metabolic changes in drug-naive, first-episode psychosis patients treated with haloperidol, olanzapine, or risperidone. J Clin Psychiatry 68:1733-1740.
51. Perfetti A, Oriente F, Iovino S, Alberobello AT, Barbagallo AP, Esposito I, Fiory F, Teperino R, Ungaro P, Miele C, Formisano P, Beguinot F. 2007. Phorbol esters induce intracellular accumulation of the anti-apoptotic protein PED/PEA-15 by preventing ubiquitinylation and proteasomal degradation. J Biol Chem 282:8648-8657.
52. Pirola L, Bonnafous S, Johnston AM, Chaussade C, Portis F, Van Obberghen E. 2003. Phosphoinositide 3-kinase-mediated reduction of insulin receptor substrate-1/2 protein expression via different mechanisms contributes to the insulin-induced desensitization of its signaling pathways in L6 muscle cells. J Biol Chem 278:15641-15651.
53. Reynolds GP. 2004. Receptor mechanisms in the treatment of schizophrenia. J Psychopharmacol 18:340-345.
54. Ryan MC, Collins P, Thakore JH. 2003. Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia. Am J Psychiatry 160:284-289.
55. Sernyak MJ, Leslie DL, Alarcon RD, Losonczy MF, Rosenheck R. 2002. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry 159:56-60.
56. Sharif A, Renault F, Beuvon F, Castellanos R, Canton B, Barbeito L, Junier MP, Chneiweiss H. 2004. The expression of PEA-15 (phosphoprotein enriched in astrocytes of 15kDa) defines subpopulations of astrocytes and neurons throughout the adult mouse brain. Neuroscience 126:263-275.
57. Stone JM, Pilowsky LS. 2007. Novel targets for drugs in schizophrenia. CNS Neurol Disord Drug Targets 6:265-272.
58. Sutton LP, Honardoust D, Mouyal J, Rajakumar N, Rushlow WJ. 2007. Activation of the canonical Wnt pathway by the antipsychotics haloperidol and clozapine involves dishevelled-3. J Neurochem 102:153-169.
59. Tajmir P, Kwan JJ, Kessas M, Mozammel S, Sweeney G. 2003. Acute and chronic leptin treatment mediate contrasting effects on signaling, glucose uptake, and GLUT4 translocation in L6- GLUT4myc myotubes. J Cell Physiol 197:122-130.
60. Thakore JH. 2005. Metabolic syndrome and schizophrenia. Br J Psychiatry 186:455-456.
61. Trencia A, Perfetti A, Cassese A, Vigliotta G, Miele C, Oriente F, Santopietro S, Giacco F, Condorelli G, Formisano P, Beguinot F. 2003. Protein kinase B/Akt binds and phosphorylates PED/PEA-15, stabilizing its antiapoptotic action. Mol Cell Biol 23:4511-4521.
62. Valentino R, Lupoli GA, Raciti GA, Oriente F, Farinaro E, Della Valle E, Salomone M, Riccardi G, Vaccaro O, Donnarumma G, Sesti G, Hribal ML, Cardellini M, Miele C, Formisano P, Beguinot F. 2006. The PEA15 gene is overexpressed and related to insulin resistance in healthy first-degree relatives of patients with type 2 diabetes. Diabetologia 49:3058-3066.
63. Vestri HS, Maianu L, Moellering DR, Garvey WT. 2007. Atypical antipsychotic drugs directly impair insulin action in adipocytes: Effects on glucose transport, lipogenesis, and antilipolysis. Neuropsychopharmacology 32:765-772.
64. Vigliotta G, Miele C, Santopietro S, Portella G, Perfetti A, Maitan MA, Cassese A, Oriente F, Trencia A, Fiory F, Romano C, Tiveron C, Tatangelo L, Troncone G, Formisano P, Beguinot F. 2004. Overexpression of the ped/pea-15 gene causes diabetes by impairing glucose-stimulated insulin secretion in addition to insulin action. Mol Cell Biol 24:5005-5015.
65. Wirshing DA, Spellberg BJ, Erhart SM, Marder SR, Wirshing WC. 1998. Novel antipsychotics and new onset diabetes. Biol Psychiatry 44:778-783.
66. Xiao C, Yang BF, Asadi N, Beguinot F, Hao C. 2002. Tumor necrosis factor-related apoptosis-inducing ligand-induced death-inducing signaling complex and its modulation by c-FLIP and PED/PEA-15 in glioma cells. J Biol Chem 277:25020-25025.