PI3K-C2α Knockdown Results in Rerouting of Insulin Signaling and Pancreatic Beta Cell Proliferation

Cell Reports

Volumn 13, Issue 1, 2015, Pages 15-22

  Leibiger, Barbara ^a   Moede, Tilo ^a   Paschen, Meike ^a   Yunn, Na Oh ^b   Lim, Jong Hoon ^b   Ryu, Sung Ho ^b   Pereira, Teresa ^a   Berggren, Per Olof ^a,b,c   Leibiger, Ingo B ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

^b Pohang University of Science and Technology (POSTECH)   (South Korea)

^c NANYANG TECHNOLOGICAL UNIVERSITY   (Singapore)

Author keywords

[No Author keywords available]

Indexed keywords

C PEPTIDE; GLUCOKINASE; INSULIN RECEPTOR; PHOSPHATIDYLINOSITOL 3 KINASE CLASS 2 ALPHA; PHOSPHATIDYLINOSITOL 4 PHOSPHATE 3 KINASE; PROTEIN P85; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; GLUCOSE; INSULIN; PHOSPHATIDYLINOSITOL 3 KINASE; PIK3C2A PROTEIN, MOUSE; PROTEIN KINASE B;

ANIMAL CELL; APOPTOSIS; ARTICLE; CELL DIFFERENTIATION; CELL PROLIFERATION; CONTROLLED STUDY; IMMUNOHISTOCHEMISTRY; IMMUNOPRECIPITATION; INSULIN RESISTANCE; INSULIN RESPONSE; NONHUMAN; ONCOGENE C FOS; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; WESTERN BLOTTING; ANIMAL; ANTAGONISTS AND INHIBITORS; CYTOLOGY; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; HUMAN; METABOLISM; MOLECULAR GENETICS; MOUSE; MOUSE MUTANT; NUCLEOTIDE SEQUENCE; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ANIMALS; BASE SEQUENCE; CELL DIFFERENTIATION; CELL LINE, TUMOR; CELL PROLIFERATION; GENE EXPRESSION REGULATION; GLUCOSE; HUMANS; INSULIN; INSULIN RESISTANCE; INSULIN-SECRETING CELLS; MICE; MICE, OBESE; MOLECULAR SEQUENCE DATA; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTOR, INSULIN; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION;

EID: 84943354035     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2015.08.058     Document Type: Article

References (34)

1. Åvall K., Ali Y., Leibiger I.B., Leibiger B., Moede T., Paschen M., Dicker A., Daré E., Köhler M., Ilegems E., et al. Apolipoprotein CIII links islet insulin resistance to β-cell failure in diabetes. Proc. Natl. Acad. Sci. USA 2015, 112:E2611-E2619.
2. 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.
3. Belfiore A., Frasca F., Pandini G., Sciacca L., Vigneri R. Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocr. Rev. 2009, 30:586-623.
4. Bernal-Mizrachi E., Wen W., Stahlhut S., Welling C.M., Permutt M.A. Islet β cell expression of constitutively active Akt1/PKB α induces striking hypertrophy, hyperplasia, and hyperinsulinemia. J. Clin. Invest. 2001, 108:1631-1638.
5. Book C.B., Dunaif A. Selective insulin resistance in the polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 1999, 84:3110-3116.
6. Brown M.S., Goldstein J.L. Selective versus total insulin resistance: a pathogenic paradox. Cell Metab. 2008, 7:95-96.
7. Campa C.C., Franco I., Hirsch E. PI3K-C2α: One enzyme for two products coupling vesicle trafficking and signal transduction. FEBS Lett. 2015, 589:1552-1558.
8. Cantley J., Choudhury A.I., Asare-Anane H., Selman C., Lingard S., Heffron H., Herrera P., Persaud S.J., Withers D.J. Pancreatic deletion of insulin receptor substrate 2 reduces beta and alpha cell mass and impairs glucose homeostasis in mice. Diabetologia 2007, 50:1248-1256.
9. Dominguez V., Raimondi C., Somanath S., Bugliani M., Loder M.K., Edling C.E., Divecha N., da Silva-Xavier G., Marselli L., Persaud S.J., et al. Class II phosphoinositide 3-kinase regulates exocytosis of insulin granules in pancreatic beta cells. J. Biol. Chem. 2011, 286:4216-4225.
10. Elis W., Triantafellow E., Wolters N.M., Sian K.R., Caponigro G., Borawski J., Gaither L.A., Murphy L.O., Finan P.M., Mackeigan J.P. Down-regulation of class II phosphoinositide 3-kinase alpha expression below a critical threshold induces apoptotic cell death. Mol. Cancer Res. 2008, 6:614-623.
11. Fatrai S., Elghazi L., Balcazar N., Cras-Méneur C., Krits I., Kiyokawa H., Bernal-Mizrachi E. Akt induces β-cell proliferation by regulating cyclin D1, cyclin D2, and p21 levels and cyclin-dependent kinase-4 activity. Diabetes 2006, 55:318-325.
12. Hashimoto N., Kido Y., Uchida T., Asahara S., Shigeyama Y., Matsuda T., Takeda A., Tsuchihashi D., Nishizawa A., Ogawa W., et al. Ablation of PDK1 in pancreatic beta cells induces diabetes as a result of loss of beta cell mass. Nat. Genet. 2006, 38:589-593.
13. Ilegems E., Dicker A., Speier S., Sharma A., Bahow A., Edlund P.K., Leibiger I.B., Berggren P.O. Reporter islets in the eye reveal the plasticity of the endocrine pancreas. Proc. Natl. Acad. Sci. USA 2013, 110:20581-20586.
14. Imai J., Katagiri H., Yamada T., Ishigaki Y., Suzuki T., Kudo H., Uno K., Hasegawa Y., Gao J., Kaneko K., et al. Regulation of pancreatic beta cell mass by neuronal signals from the liver. Science 2008, 322:1250-1254.
15. Jiang Z.Y., Lin Y.W., Clemont A., Feener E.P., Hein K.D., Igarashi M., Yamauchi T., White M.F., King G.L. Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats. J. Clin. Invest. 1999, 104:447-457.
16. Kang S., Song J., Kang J., Kang H., Lee D., Lee Y., Park D. Suppression of the alpha-isoform of class II phosphoinositide 3-kinase gene expression leads to apoptotic cell death. Biochem. Biophys. Res. Commun. 2005, 329:6-10.
17. Kubota N., Terauchi Y., Tobe K., Yano W., Suzuki R., Ueki K., Takamoto I., Satoh H., Maki T., Kubota T., et al. Insulin receptor substrate 2 plays a crucial role in β cells and the hypothalamus. J. Clin. Invest. 2004, 114:917-927.
18. Kulkarni R.N. New insights into the roles of insulin/IGF-I in the development and maintenance of β-cell mass. Rev. Endocr. Metab. Disord. 2005, 6:199-210.
19. Leibiger B., Leibiger I.B., Moede T., Kemper S., Kulkarni R.N., Kahn C.R., de Vargas L.M., Berggren P.O. Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic β cells. Mol. Cell 2001, 7:559-570.
20. Leibiger I.B., Leibiger B., Berggren P.O. Insulin signaling in the pancreatic beta-cell. Annu. Rev. Nutr. 2008, 28:233-251.
21. Leibiger B., Moede T., Uhles S., Barker C.J., Creveaux M., Domin J., Berggren P.O., Leibiger I.B. Insulin-feedback via PI3K-C2α activated PKBalpha/Akt1 is required for glucose-stimulated insulin secretion. FASEB J. 2010, 24:1824-1837.
22. Leibiger I.B., Brismar K., Berggren P.O. Novel aspects on pancreatic beta-cell signal-transduction. Biochem. Biophys. Res. Commun. 2010, 396:111-115.
23. Li S., Brown M.S., Goldstein J.L. Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis. Proc. Natl. Acad. Sci. USA 2010, 107:3441-3446.
24. Lindström P. The physiology of obese-hyperglycemic mice [ob/ob mice]. ScientificWorldJournal 2007, 7:666-685.
25. Liu Y., Mziaut H., Ivanova A., Solimena M. beta-Cells at the crossroads: choosing between insulin granule production and proliferation. Diabetes Obes. Metab. 2009, 11(Suppl 4):54-64.
26. Ng S.K., Neo S.Y., Yap Y.W., Karuturi R.K., Loh E.S., Liau K.H., Ren E.C. Ablation of phosphoinositide-3-kinase class II alpha suppresses hepatoma cell proliferation. Biochem. Biophys. Res. Commun. 2009, 387:310-315.
27. Okada T., Liew C.W., Hu J., Hinault C., Michael M.D., Krtzfeldt J., Yin C., Holzenberger M., Stoffel M., Kulkarni R.N. Insulin receptors in beta-cells are critical for islet compensatory growth response to insulin resistance. Proc. Natl. Acad. Sci. USA 2007, 104:8977-8982.
28. Okamoto H., Hribal M.L., Lin H.V., Bennett W.R., Ward A., Accili D. Role of the forkhead protein FoxO1 in beta cell compensation to insulin resistance. J. Clin. Invest. 2006, 116:775-782.
29. Pandolfi A., Solini A., Pellegrini G., Mincione G., Di Silvestre S., Chiozzi P., Giardinelli A., Di Marcantonio M.C., Piccirelli A., Capani F., Consoli A. Selective insulin resistance affecting nitric oxide release but not plasminogen activator inhibitor-1 synthesis in fibroblasts from insulin-resistant individuals. Arterioscler. Thromb. Vasc. Biol. 2005, 25:2392-2397.
30. Terauchi Y., Takamoto I., Kubota N., Matsui J., Suzuki R., Komeda K., Hara A., Toyoda Y., Miwa I., Aizawa S., et al. Glucokinase and IRS-2 are required for compensatory beta cell hyperplasia in response to high-fat diet-induced insulin resistance. J. Clin. Invest. 2007, 117:246-257.
31. Uhles S., Moede T., Leibiger B., Berggren P.O., Leibiger I.B. Isoform-specific insulin receptor signaling involves different plasma membrane domains. J. Cell Biol. 2003, 163:1327-1337.
32. Uhles S., Moede T., Leibiger B., Berggren P.O., Leibiger I.B. Selective gene activation by spatial segregation of insulin receptor B signaling. FASEB J. 2007, 21:1609-1621.
33. Vasavada R.C., Gonzalez-Pertusa J.A., Fujinaka Y., Fiaschi-Taesch N., Cozar-Castellano I., Garcia-Ocaña A. Growth factors and beta cell replication. Int. J. Biochem. Cell Biol. 2006, 38:931-950.
34. Yesil P., Lammert E. Islet dynamics: a glimpse at beta cell proliferation. Histol. Histopathol. 2008, 23:883-895.