LKB1 and AMPK differentially regulate pancreatic β-cell identity

FASEB Journal

Volumn 28, Issue 11, 2014, Pages 4972-4985

  Kone, Marina ^a   Pullen, Timothy J ^a   Sun, Gao ^a   Ibberson, Mark ^d   Martinez Sanchez, Aida ^a   Sayers, Sophie ^a   Nguyen Tu, Marie Sophie ^a   Kantor, Chase ^a   Swisa, Avital ^e   Dor, Yuval ^e   Gorman, Tracy ^f   Ferrer, Jorge ^b   Thorens, Bernard ^d   Reimann, Frank ^g   Gribble, Fiona ^g   McGinty, James A ^c   Chen, Lingling ^c   French, Paul M ^c   Birzele, Fabian ^h   Hildebrandt, Tobias ^h   Uphues, Ingo ^h   Rutter, Guy A ^a   more..

^a Section of Cell Biology   (United Kingdom)

^b Section of b Cell Development Division of Diabetes Department of Medicine   (United Kingdom)

^c IMPERIAL COLLEGE LONDON   (United Kingdom)

^d UNIVERSITY OF LAUSANNE   (Switzerland)

^e HEBREW UNIVERSITY OF JERUSALEM   (Israel)

^f ASTRAZENECA   (United Kingdom)

^g UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^h BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

Author keywords

Diabetes; Insulin secretion; Islet; RNASeq

Indexed keywords

ALBUMIN; ARX PROTEIN; CARTPT PROTEIN; CRE RECOMBINASE; DLGAP2 PROTEIN; ELONGATION OF VERY LONG CHAIN FATTY ACIDS 2; G PROTEIN COUPLED RECEPTOR; GCG PROTEIN; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; GLUCOSE TRANSPORTER 2; GLUTAMIC ACID; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; HYPOXIA INDUCIBLE FACTOR 1; IODIDE PEROXIDASE; LIVER KINASE B1; MGST1 PROTEIN; MONOCARBOXYLATE TRANSPORTER 1; NEUROGENIC DIFFERENTIATION FACTOR; NPTX2 PROTEIN; PCSK1 PROTEIN; PDYN PROTEIN; PROPROTEIN CONVERTASE 2; PROTEIN KINASE; SOMATOSTATIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR MAFA; TRANSCRIPTION FACTOR NKX6.2; TRANSCRIPTION FACTOR PDX 1; UNCLASSIFIED DRUG; VERY LONG CHAIN FATTY ACID; INSULIN; PROTEIN SERINE THREONINE KINASE; STK11 PROTEIN, MOUSE;

ADULT; ANIMAL CELL; APOPTOSIS; ARTICLE; BINDING SITE; BLADDER CANCER; CELL DIFFERENTIATION; CELL ENERGY; CELL SIZE; CELL VOLUME; COLORECTAL CANCER; CONTROLLED STUDY; DNA REPLICATION; DOWN REGULATION; ENZYME ACTIVATION; ENZYME ACTIVE SITE; ENZYME ACTIVITY; GENE CLUSTER; GENE CONTROL; GENE DELETION; GENE EXPRESSION; GENE IDENTIFICATION; GENE REPRESSION; GENETIC ASSOCIATION; GLIOMA; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE TOLERANCE; HOUSEKEEPING GENE; IMMUNOCYTOCHEMISTRY; IN VITRO STUDY; INSULIN RELEASE; INSULIN SENSITIVITY; MALE; MELANOMA; MICROARRAY ANALYSIS; MOUSE; NERVE CELL DIFFERENTIATION; NONHUMAN; PANCREAS CANCER; PANCREAS ISLET BETA CELL; POSTSYNAPTIC DENSITY; PROMOTER REGION; PROTEIN DEGRADATION; PROTEIN DEPLETION; REGULATORY MECHANISM; RIBOSOME; SECOND MESSENGER; SINGLE NUCLEOTIDE POLYMORPHISM; SKELETAL MUSCLE; SMALL INTESTINE; SPLICEOSOME; STOMACH; SYNAPTIC TRANSMISSION; SYNAPTOGENESIS; TARGET CELL; UPREGULATION; WEIGHT GAIN; ANIMAL; C57BL MOUSE; ENZYMOLOGY; METABOLISM; NON INSULIN DEPENDENT DIABETES MELLITUS; PHYSIOLOGY; SIGNAL TRANSDUCTION;

AMP-ACTIVATED PROTEIN KINASES; ANIMALS; DIABETES MELLITUS, TYPE 2; INSULIN; INSULIN-SECRETING CELLS; MICE, INBRED C57BL; PROTEIN-SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION;

EID: 84912006450     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.14-257667     Document Type: Article

References (65)

1. Scully, T. (2012) Diabetes in numbers. Nature 485, S2-S3
2. Rutter, G. A., and Parton, L. E. (2008) The beta-cell in type 2 diabetes and in obesity. Front. Horm. Res. 36, 118-134
3. Rutter, G. A. (2001) Nutrient-secretion coupling in the pancreatic islet β-cell: recent advances. Mol. Aspects Med. 22, 247-284
4. Butler, A. E., Janson, J., Bonner-Weir, S., Ritzel, R., Rizza, R. A., and Butler, P. C. (2003) Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 52, 102-110
5. Rahier, J., Guiot, Y., Goebbels, R. M., Sempoux, C., and Henquin, J. C. (2008) Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes. Metab. 10, 32-42
6. Jonas, J. C., Sharma, A., Hasenkamp, W., Ilkova, H., Patane, G., Laybutt, R., Bonner-Weir, S., and Weir, G. C. (1999) Chronic hyperglycemia triggers loss of pancreatic beta cell differentiation in an animal model of diabetes. J. Biol. Chem. 274, 14112-14121
7. Del Guerra, S., Lupi, R., Marselli, L., Masini, M., Bugliani, M., Sbrana, S., Torri, S., Pollera, M., Boggi, U., Mosca, F., Del Prato, S., and Marchetti, P. (2005) Functional and molecular defects of pancreatic islets in human type 2 diabetes. Diabetes 54, 727-735
8. Talchai, C., Xuan, S., Lin, H. V., Sussel, L., and Accili, D. (2012) Pancreatic beta cell dedifferentiation as a mechanism of diabetic beta cell failure. Cell 150, 1223-1234
9. Pullen, T. J., Khan, A. M., Barton, G., Butcher, S. A., Sun, G., and Rutter, G. A. (2010) Identification of genes selectively disallowed in the pancreatic islet. Islets 2, 89-95
10. Pullen, T. J., and Rutter, G. A. (2013) When less is more: the forbidden fruits of gene repression in the adult beta-cell. Diabetes Obes. Metab. 15, 503-512
11. Pullen, T. J., Sylow, L., Sun, G., Halestrap, A. P., Richter, E. A., and Rutter, G. A. (2012) Over-expression of Monocarboxylate Transporter-1 (Slc16a1) in the pancreatic â-cell leads to relative hyperinsulinism during exercise. Diabetes 61, 1725
12. Partanen, J. I., Tervonen, T. A., and Klefstrom, J. (2013) Breaking the epithelial polarity barrier in cancer: the strange case of LKB1/PAR-4. Philos. Trans. R. Soc. Lond. B Biol. Sci. 368, 20130111
13. Momcilovic, M., Hong, S. P., and Carlson, M. (2006) Mammalian TAK1 activates Snf1 protein kinase in yeast and phosphorylates AMP-activated protein kinase in vitro. J. Biol. Chem. 281, 25336-25343
14. Hawley, S. A., Boudeau, J., Reid, J. L., Mustard, K. J., Udd, L., Makela, T. P., Alessi, D. R., and Hardie, D. G. (2003) Complexes between the LKB1 tumor suppressor, STRADalpha/beta and MO25alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J. Biol. 2, 28
15. Woods, A., Johnstone, S. R., Dickerson, K., Leiper, F. C., Fryer, L. G., Neumann, D., Schlattner, U., Wallimann, T., Carlson, M., and Carling, D. (2003) LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr. Biol. 13, 2004-2008
16. Lizcano, J. M., Goransson, O., Toth, R., Deak, M., Morrice, N. A., Boudeau, J., Hawley, S. A., Udd, L., Makela, T. P., Hardie, D. G., and Alessi, D. R. (2004) LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/ PAR-1. EMBO J. 23, 833-843
17. Rutter, G. A., daSilvaXavier, G., and Leclerc, I. (2003) Roles of 5=-AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis. Biochem. J. 375, 1-16
18. Rutter, G. A., and Leclerc, I. (2009) The AMP-regulated kinase family: enigmatic targets for diabetes therapy. Mol. Cell. Endocrinol. 297, 41-49
19. Jenne, D. E., Reimann, H., Nezu, J., Friedel, W., Loff, S., Jeschke, R., Muller, O., Back, W., and Zimmer, M. (1998) Peutz-Jeghers syndrome is caused by mutations in a novel serine threonine kinase. Nat. Genet. 18, 38-43
20. Sun, G., Tarasov, A. I., McGinty, J. A., French, P. M., McDonald, A., Leclerc, I., and Rutter, G. A. (2010) LKB1 deletion with the RIP. Cre-transgene modifies pancreatic-cell morphology and enhances insulin secretion in vivo. Am. J. Physiol. Endocrinol. Metab. 298, E1261-E1273
21. Granot, Z., Swisa, A., Magenheim, J., Stolovich-Rain, M., Fujimoto, W., Manduchi, E., Miki, T., Lennerz, J. K., Stoeckert, C. J., Jr., Meyuhas, O., Seino, S., Permutt, M. A., Piwnica-Worms, H., Bardeesy, N., and Dor, Y. (2009) LKB1 regulates pancreatic beta cell size, polarity, and function. Cell Metab. 10, 296-308
22. Fu, A., Ng, A. C., Depatie, C., Wijesekara, N., He, Y., Wang, G. S., Bardeesy, N., Scott, F. W., Touyz, R. M., Wheeler, M. B., and Screaton, R. A. (2009) Loss of Lkb1 in adult beta cells increases beta cell mass and enhances glucose tolerance in mice. Cell Metab. 10, 285-295
23. Sun, G., Tarasov, A. I., McGinty, J., McDonald, A., DaSilva Xavier, G., Gorman, T., Marley, A., French, P. M., Parker, H., Gribble, F., Reimann, F., Prendiville, O., Carzaniga, R., Viollet, B., Leclerc, I., and Rutter, G. A. (2010) Ablation of AMPactivated protein kinase alpha1 and alpha2 from pancreatic beta-cells and RIP. Cre neurons suppresses insulin release in vivo. Diabetologia 53, 924-936
24. Beall, C., Piipari, K., Al-Qassab, H., Smith, M. A., Parker, N., Carling, D., Viollet, B., Withers, D. J., and Ashford, M. L. (2010) Loss of AMP-activated protein kinase alpha2 subunit in mouse beta-cells impairs glucose-stimulated insulin secretion and inhibits their sensitivity to hypoglycaemia. Biochem. J. 429, 323-333
25. Wicksteed, B., Brissova, M., Yan, W., Opland, D. M., Plank, J. L., Reinert, R. B., Dickson, L. M., Tamarina, N. A., Philipson, L. H., Shostak, A., Bernal-Mizrachi, E., Elghazi, L., Roe, M. W., Labosky, P. A., Myers, M. M., Jr., Gannon, M., Powers, A. C., and Dempsey, P. J. (2010) Conditional gene targeting in mouse pancreatic {beta}-cells: analysis of ectopic Cre transgene expression in the brain. Diabetes 59, 3090-3098
26. Tamarina, N. A., Roe, M. W., and Philipson, L. (2014) Characterization of mice expressing Ins1 gene promoter driven Cre-ERT recombinase for conditional gene deletion in pancreatic beta-cells. [E-pub ahead of print] Islets 6, doi: 10.4161/isl.27685
27. Bardeesy, N., Sinha, M., Hezel, A. F., Signoretti, S., Hathaway, N. A., Sharpless, N. E., Loda, M., Carrasco, D. R., and DePinho, R. A. (2002) Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation. Nature 419, 162-167
28. Ravier, M. A., and Rutter, G. A. (2010) Isolation and culture of mouse pancreatic islets for ex vivo imaging studies with trappable or recombinant fluorescent probes. Methods Mol. Biol. 633, 171-184
29. Stange, G., Van De Casteele, M., and Heimberg, H. (2003) Purification of rat pancreatic B-cells by fluorescence-activated cell sorting. Methods Mol. Med. 83, 15-22
30. Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., and Salzberg, S. L. (2013) TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36
31. Vencio, R. Z., Brentani, H., Patrao, D. F., and Pereira, C. A. (2004) Bayesian model accounting for within-class biological variability in Serial Analysis of Gene Expression (SAGE). BMC Bioinformatics 5, 119
32. Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., and Wold, B. (2008) Mapping and quantifying mammalian transcriptomes by RNA-seq. Nat. Methods. 5, 621-628
33. Zambon, A. C., Zhang, L., Minovitsky, S., Kanter, J. R., Prabhakar, S., Salomonis, N., Vranizan, K., Dubchak, I., Conklin, B. R., and Insel, P. A. (2005) Gene expression patterns define key transcriptional events in cell-cycle regulation by cAMP and protein kinase A. Proc. Natl. Acad. Sci. U. S. A. 102, 8561-8566
34. Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., and Mesirov, J. P. (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. U. S. A. 102, 15545-15550
35. Gentleman, R. C., Carey, V. J., Bates, D. M., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J., Hornik, K., Hothorn, T., Huber, W., Iacus, S., Irizarry, R., Leisch, F., Li, C., Maechler, M., Rossini, A. J., Sawitzki, G., Smith, C., Smyth, G., Tierney, L., Yang, J. Y., and Zhang, J. (2004) Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 5, R80
36. Ravier, M. A., and Rutter, G. A. (2005) Glucose or insulin, but not zinc ions, inhibit glucagon secretion from mouse pancreatic β-cells. Diabetes 54, 1789-1797
37. 2+ uniporter MCU is essential for glucoseinduced ATP increases in pancreatic β-cells. PLoS ONE 7, e39722
38. Edelstein, A., Amodaj, N., Hoover, K., Vale, R., and Stuurman, N. (2010) Computer control of microscopes using μManager. Curr. Protoc. Mol. Biol. 92, 14.20.1-14.20.17
39. Sun, G., Reynolds, R., Leclerc, I., and Rutter, G. A. (2010) RIP2-mediated LKB1 deletion causes axon degeneration in the spinal cord and hind-limb paralysis. Dis. Models Mech. 4, 193-202
40. Rother, E., Belgardt, B. F., Tsaousidou, E., Hampel, B., Waisman, A., Myers, M. G., Jr., and Bruning, J. C. (2012) Acute selective ablation of rat insulin promoter-expressing (RIPHER) neurons defines their orexigenic nature. Proc. Natl. Acad. Sci. U.S.A. 109, 18132-18137
41. Courtney, M., Gjernes, E., Druelle, N., Ravaud, C., Vieira, A., Ben-Othman, N., Pfeifer, A., Avolio, F., Leuckx, G., Lacas-Gervais, S., Burel-Vandenbos, F., Ambrosetti, D., Hecksher-Sorensen, J., Ravassard, P., Heimberg, H., Mansouri, A., and Collombat, P. (2013) The inactivation of Arx in pancreatic alpha-cells triggers their neogenesis and conversion into functional beta-like cells. PLoS Genet. 9, e1003934
42. Bramswig, N. C., Everett, L. J., Schug, J., Dorrell, C., Liu, C., Luo, Y., Streeter, P. R., Naji, A., Grompe, M., and Kaestner, K. H. (2013) Epigenomic plasticity enables human pancreatic alpha to beta cell reprogramming. J. Clin. Invest. 123, 1275-1284
43. Thorens, B., Sarkar, H. K., Kaback, H. R., and Lodish, H. F. (1988) Cloning and functional expression in bacteria of a novel glucose transporter present in liver intestine kidney and B-pancreatic islet cells. Cell 55, 281-290
44. Palmer, C. L., Cotton, L., and Henley, J. M. (2005) The molecular pharmacology and cell biology of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Pharmacol. Rev. 57, 253-277
45. Takeuchi, M., Hata, Y., Hirao, K., Toyoda, A., Irie, M., and Takai, Y. (1997) SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density. J. Biol. Chem. 272, 11943-11951
46. Thorrez, L., Laudadio, I., Van, D. K., Quintens, R., Hendrickx, N., Granvik, M., Lemaire, K., Schraenen, A., Van, L. L., Lehnert, S., Guayo-Mazzucato, C., Cheng-Xue, R., Gilon, P., Van, M. I., Bonner-Weir, S., Lemaigre, F., and Schuit, F. (2011) Tissuespecific disallowance of housekeeping genes: the other face of cell differentiation. Genome Res. 21, 95-105
47. Reimann, F., Habib, A. M., Tolhurst, G., Parker, H. E., Rogers, G. J., and Gribble, F. M. (2008) Glucose-sensing in L-cells: a primary cell study. Cell Metab. 8, 532-539
48. Da Silva Xavier, G., Bellomo, E. A., McGinty, J. A., French, P. M., and Rutter, G. A. (2013) Animal models of GWAS-identified type 2 diabetes genes. J. Diabetes Res. 2013, 906590
49. Chen, G., and Courey, A. J. (2000) Groucho/TLE family proteins and transcriptional repression. Gene 249, 1-16
50. Upadhyay, G., Goessling, W., North, T. E., Xavier, R., Zon, L. I., and Yajnik, V. (2008) Molecular association between betacatenin degradation complex and Rac guanine exchange factor DOCK4 is essential for Wnt/beta-catenin signaling. Oncogene 27, 5845-5855
51. Jacob, L. S., Wu, X., Dodge, M. E., Fan, C. W., Kulak, O., Chen, B., Tang, W., Wang, B., Amatruda, J. F., and Lum, L. (2011) Genome-wide RNAi screen reveals disease-associated genes that are common to Hedgehog and Wnt signaling. Sci. Signal. 4, ra4
52. Marselli, L., Thorne, J., Dahiya, S., Sgroi, D. C., Sharma, A., Bonner-Weir, S., Marchetti, P., and Weir, G. C. (2010) Gene expression profiles of beta-cell enriched tissue obtained by laser capture microdissection from subjects with type 2 diabetes. PLoS ONE 5, e11499
53. Kawashima, H., Sugito, K., Yoshizawa, S., Uekusa, S., Furuya, T., Ikeda, T., Koshinaga, T., Shinojima, Y., Hasegawa, R., Mishra, R., Igarashi, J., Kimura, M., Wang, X., Fujiwara, K., Gosh, S., and Nagase, H. (2012) DNA hypomethylation at the ZNF206-exon 5 CpG island associated with neuronal differentiation in mice and development of neuroblastoma in humans. Int. J. Oncol. 40, 31-39
54. De Saedeleer, C. J., Porporato, P. E., Copetti, T., Perez-Escuredo, J., Payen, V. L., Brisson, L., Feron, O., and Sonveaux, P. (2013) Glucose deprivation increases monocarboxylate transporter 1 (MCT1) expression and MCT1-dependent tumor cell migration. [E-pub ahead of print] Oncogene doi: 10.1038/ onc.2013.454
55. Nie, J., Liu, X., Lilley, B. N., Zhang, H., Pan, Y. A., Kimball, S. R., Zhang, J., Zhang, W., Wang, L., Jefferson, L. S., Sanes, J. R., Han, X., and Shi, Y. (2013) SAD-A kinase controls islet beta-cell size and function as a mediator of mTORC1 signaling. Proc. Natl. Acad. Sci. U. S. A. 110, 13857-13862
56. Sakamaki, J. I., Fu, A., Reeks, C., Baird, S., Depatie, C., Al, A. M., Bardeesy, N., Gingras, A. C., Yee, S. P., and Screaton, R. A. (2014) Role of the SIK2-p35-PJA2 complex in pancreatic betacell functional compensation. Nat. Cell Biol. 16, 234-244
57. Ishii, K., Kanatsu-Shinohara, M., Toyokuni, S., and Shinohara, T. (2012) FGF2 mediates mouse spermatogonial stem cell self-renewal via upregulation of Etv5 and Bcl6b through MAP2K1 activation. Development 139, 1734-1743
58. de Lau, W. B., Snel, B., and Clevers, H. C. (2012) The R-spondin protein family. Genome Biol. 13, 242-213
59. Fromer, M., Pocklington, A. J., Kavanagh, D. H., Williams, H. J., Dwyer, S., Gormley, P., Georgieva, L., Rees, E., Palta, P., Ruderfer, D. M., Carrera, N., Humphreys, I., Johnson, J. S., Roussos, P., Barker, D. D., Banks, E., Milanova, V., Grant, S. G., Hannon, E., Rose, S. A., Chambert, K., Mahajan, M., Scolnick, E. M., Moran, J. L., Kirov, G., Palotie, A., McCarroll, S. A., Holmans, P., Sklar, P., Owen, M. J., Purcell, S. M., and O'Donovan, M. C. (2014) De novo mutations in schizophrenia implicate synaptic networks. Nature 506, 179-184
60. Ahmed, S., Goh, W. I., and Bu, W. (2010) I-BAR domains, IRSp53 and filopodium formation. Semin. Cell. Dev. Biol. 21, 350-356
61. Zhu, M. X. (2005) Multiple roles of calmodulin and other Ca(2+)-binding proteins in the functional regulation of TRP channels. Pflügers Arch. 451, 105-115
62. Martin, D., Allagnat, F., Chaffard, G., Caille, D., Fukuda, M., Regazzi, R., Abderrahmani, A., Waeber, G., Meda, P., Maechler, P., and Haefliger, J. A. (2008) Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells. Diabetologia 51, 1429-1439
63. Sia, G. M., Beique, J. C., Rumbaugh, G., Cho, R., Worley, P. F., and Huganir, R. L. (2007) Interaction of the N-terminal domain of the AMPA receptor GluR4 subunit with the neuronal pentraxin NP1 mediates GluR4 synaptic recruitment. Neuron 55, 87-102
64. Crombag, H. S., Dickson, M., Dinenna, M., Johnson, A. W., Perin, M. S., Holland, P. C., Baraban, J. M., and Reti, I. M. (2009) Narp deletion blocks extinction of morphine place preference conditioning. Neuropsychopharmacology 34, 857-866
65. Laybutt, D. R., Glandt, M., Xu, G., Ahn, Y. B., Trivedi, N., Bonner-Weir, S., and Weir, G. C. (2003) Critical reduction in beta-cell mass results in two distinct outcomes over time. Adaptation with impaired glucose tolerance or decompensated diabetes. J. Biol. Chem. 278, 2997-3005