BibTex format

author = {Kone, M and Sun, G and Ibberson, M and Martinez-Sanchez, A and Sayers, S and Marie-Sophie, N-T and Kantor, C and Swisa, A and Dor, Y and Gorman, T and Ferrer, J and Thorens, B and Reimann, F and Gribble, F and McGinty, JA and Chen, L and French, PM and Birzele, F and Hildebrandt, T and Uphues, I and Rutter, GA},
doi = {10.1096/fj.14-257667},
journal = {Faseb Journal},
pages = {4972--4985},
title = {LKB1 and AMPK differentially regulate pancreatic beta-cell identity},
url = {},
volume = {28},
year = {2014}

RIS format (EndNote, RefMan)

AB - Fully differentiated pancreatic b cellsare essential for normal glucose homeostasis in mammals.Dedifferentiation of these cells has been suggestedto occur in type 2 diabetes, impairing insulinproduction. Since chronic fuel excess (“glucotoxicity”)is implicated in this process, we sought here to identifythe potential roles in b-cell identity of the tumor suppressorliver kinase B1 (LKB1/STK11) and the downstreamfuel-sensitive kinase, AMP-activated proteinkinase (AMPK). Highly b-cell-restricted deletion ofeach kinase in mice, using an Ins1-controlled Cre, wastherefore followed by physiological, morphometric,and massive parallel sequencing analysis. Loss of LKB1strikingly (2.0–12-fold, E<0.01) increased the expressionof subsets of hepatic (Alb, Iyd, Elovl2) and neuronal(Nptx2, Dlgap2, Cartpt, Pdyn) genes, enhancing glutamatesignaling. These changes were partially recapitulatedby the loss of AMPK, which also up-regulated b-cell“disallowed” genes (Slc16a1, Ldha, Mgst1, Pdgfra) 1.8- to3.4-fold (E<0.01). Correspondingly, targeted promoterswere enriched for neuronal (Zfp206; P51.3310233)and hypoxia-regulated (HIF1; P52.5310216) transcriptionfactors. In summary, LKB1 and AMPK, through onlypartly overlapping mechanisms, maintain b-cell identityby suppressing alternate pathways leading to neuronal,hepatic, and other characteristics. Selective targetingof these enzymes may provide a new approach tomaintaining b-cell function in some forms of diabetes.—Kone,M., Pullen, T. J., Sun, G., Ibberson, M.,Martinez-Sanchez, A., Sayers, S., Nguyen-Tu, M.-S.,Kantor, C., Swisa, A., Dor, Y., Gorman, T., Ferrer, J.,Thorens, B., Reimann, F., Gribble, F., McGinty, J. A.,Chen, L., French, P. M., Birzele, F., Hildebrandt, T.,Uphues, I., Rutter, G. A. LKB1 and AMPK differentiallyregulate pancreatic b-cell identity.
AU - Kone,M
AU - Sun,G
AU - Ibberson,M
AU - Martinez-Sanchez,A
AU - Sayers,S
AU - Marie-Sophie,N-T
AU - Kantor,C
AU - Swisa,A
AU - Dor,Y
AU - Gorman,T
AU - Ferrer,J
AU - Thorens,B
AU - Reimann,F
AU - Gribble,F
AU - McGinty,JA
AU - Chen,L
AU - French,PM
AU - Birzele,F
AU - Hildebrandt,T
AU - Uphues,I
AU - Rutter,GA
DO - 10.1096/fj.14-257667
EP - 4985
PY - 2014///
SN - 1530-6860
SP - 4972
TI - LKB1 and AMPK differentially regulate pancreatic beta-cell identity
T2 - Faseb Journal
UR -
UR -
VL - 28
ER -