0 19 Glycation-dependent glycation-dependent JJ 19 20 , , , 21 29 reactive reactive JJ 30 36 oxygen oxygen NN 37 53 species-mediated species-mediated JJ 54 65 suppression suppression NN 66 68 of of IN 69 72 the the DT 73 80 insulin insulin NN 81 85 gene gene NN 86 94 promoter promoter NN 95 103 activity activity NN 104 106 in in IN 107 110 HIT hit NN 111 116 cells cell NNS 116 117 . . . 119 128 Prolonged prolong VBN 129 133 poor poor JJ 134 142 glycemic glycemic JJ 143 150 control control NN 151 153 in in IN 154 175 non-insulin-dependent non-insulin-dependent JJ 176 184 diabetes diabetes NN 185 193 mellitus mellitus NN 194 202 patients patient NNS 203 208 often often RB 209 214 leads lead VBZ 215 217 to to TO 218 219 a a DT 220 227 decline decline NN 228 230 in in IN 231 238 insulin insulin NN 239 248 secretion secretion NN 249 253 from from IN 254 264 pancreatic pancreatic JJ 265 269 beta beta NN 270 275 cells cell NNS 275 276 , , , 277 288 accompanied accompany VBN 289 291 by by IN 292 293 a a DT 294 302 decrease decrease NN 303 305 in in IN 306 309 the the DT 310 317 insulin insulin NN 318 325 content content NN 326 328 of of IN 329 332 the the DT 333 338 cells cell NNS 338 339 . . . 340 342 As as IN 343 344 a a DT 345 349 step step NN 350 356 toward toward IN 357 368 elucidating elucidate VBG 369 372 the the DT 373 391 pathophysiological pathophysiological JJ 392 402 background background NN 403 405 of of IN 406 409 the the DT 410 419 so-called so-called JJ 420 427 glucose glucose NN 428 436 toxicity toxicity NN 437 439 to to TO 440 450 pancreatic pancreatic JJ 451 455 beta beta NN 456 461 cells cell NNS 461 462 , , , 463 465 we we PRP 466 473 induced induce VBD 474 483 glycation glycation NN 484 486 in in IN 487 494 HIT-T15 hit-t15 NN 495 500 cells cell NNS 501 506 using use VBG 507 508 a a DT 509 514 sugar sugar NN 515 519 with with IN 520 526 strong strong JJ 527 538 deoxidizing deoxidizing NN 539 547 activity activity NN 547 548 , , , 549 557 D-ribose D-ribose NNP 557 558 , , , 559 562 and and CC 563 571 examined examine VBD 572 575 the the DT 576 583 effects effect NNS 584 586 on on IN 587 594 insulin insulin NN 595 599 gene gene NN 600 613 transcription transcription NN 613 614 . . . 615 618 The the DT 619 626 results result NNS 627 629 of of IN 630 638 reporter reporter NN 639 643 gene gene NN 644 652 analyses analysis NNS 653 661 revealed reveal VBD 662 666 that that IN 667 670 the the DT 671 678 insulin insulin NN 679 683 gene gene NN 684 692 promoter promoter NN 693 695 is be VBZ 696 700 more more RBR 701 710 sensitive sensitive JJ 711 713 to to TO 714 723 glycation glycation NN 724 728 than than IN 729 732 the the DT 733 740 control control NN 741 751 beta-actin beta-actin NN 752 756 gene gene NN 757 765 promoter promoter NN 765 766 ; ; : 767 780 approximately approximately RB 781 783 50 50 CD 784 787 and and CC 788 790 80 80 CD 790 791 % % NN 792 794 of of IN 795 798 the the DT 799 806 insulin insulin NN 807 811 gene gene NN 812 820 promoter promoter NN 821 829 activity activity NN 830 833 was be VBD 834 838 lost lose VBN 839 843 when when WRB 844 847 the the DT 848 853 cells cell NNS 854 858 were be VBD 859 863 kept keep VBN 864 867 for for IN 868 869 3 3 CD 870 871 d d NN 872 874 in in IN 875 878 the the DT 879 887 presence presence NN 888 890 of of IN 891 893 40 40 CD 894 897 and and CC 898 900 60 60 CD 901 903 mM mm NN 904 912 D-ribose D-ribose NNP 912 913 , , , 914 926 respectively respectively RB 926 927 . . . 928 930 In in IN 931 940 agreement agreement NN 941 945 with with IN 946 950 this this DT 950 951 , , , 952 960 decrease decrease NN 961 963 in in IN 964 967 the the DT 968 975 insulin insulin NN 976 980 mRNA mrna NN 981 984 and and CC 985 992 insulin insulin NN 993 1000 content content NN 1001 1004 was be VBD 1005 1013 observed observe VBN 1014 1016 in in IN 1017 1020 the the DT 1021 1038 glycation-induced glycation-induced JJ 1039 1044 cells cell NNS 1044 1045 . . . 1046 1050 Also also RB 1050 1051 , , , 1052 1055 gel gel NN 1056 1064 mobility mobility NN 1065 1070 shift shift NN 1071 1079 analyses analysis NNS 1080 1085 using use VBG 1086 1094 specific specific JJ 1095 1104 antiserum antiserum NN 1105 1113 revealed reveal VBD 1114 1122 decrease decrease NN 1123 1125 in in IN 1126 1129 the the DT 1130 1141 DNA-binding dna-binding JJ 1142 1150 activity activity NN 1151 1153 of of IN 1154 1156 an an DT 1157 1164 insulin insulin NN 1165 1169 gene gene NN 1170 1183 transcription transcription NN 1184 1190 factor factor NN 1190 1191 , , , 1192 1208 PDX-1/IPF1/STF-1 PDX-1/IPF1/STF-1 NNP 1208 1209 . . . 1210 1215 These these DT 1216 1223 effects effect NNS 1224 1226 of of IN 1227 1235 D-ribose D-ribose NNP 1236 1242 seemed seem VBD 1243 1249 almost almost RB 1250 1262 irreversible irreversible JJ 1263 1266 but but CC 1267 1272 could could MD 1273 1275 be be VB 1276 1285 prevented prevent VBN 1286 1288 by by IN 1289 1297 addition addition NN 1298 1300 of of IN 1301 1302 1 1 CD 1303 1305 mM mm NN 1306 1320 aminoguanidine aminoguanidine NN 1321 1323 or or CC 1324 1326 10 10 CD 1327 1329 mM mM NNP 1330 1346 N-acetylcysteine N-acetylcysteine NNP 1346 1347 , , , 1348 1352 thus thus RB 1353 1363 suggesting suggest VBG 1364 1368 that that IN 1369 1378 glycation glycation NN 1379 1382 and and CC 1383 1391 reactive reactive JJ 1392 1398 oxygen oxygen NN 1399 1406 species specie NNS 1406 1407 , , , 1408 1417 generated generate VBN 1418 1425 through through IN 1426 1429 the the DT 1430 1439 glycation glycation NN 1440 1448 reaction reaction NN 1448 1449 , , , 1450 1455 serve serve VBP 1456 1458 as as IN 1459 1468 mediators mediator NNS 1469 1471 of of IN 1472 1475 the the DT 1476 1485 phenomena phenomenon NNS 1485 1486 . . . 1487 1492 These these DT 1493 1505 observations observation NNS 1506 1513 suggest suggest VBP 1514 1518 that that IN 1519 1526 protein protein NN 1527 1536 glycation glycation NN 1537 1539 in in IN 1540 1550 pancreatic pancreatic JJ 1551 1555 beta beta NN 1556 1561 cells cell NNS 1561 1562 , , , 1563 1568 which which WDT 1569 1575 occurs occur VBZ 1576 1578 in in FW 1579 1583 vivo vivo FW 1584 1589 under under IN 1590 1597 chronic chronic JJ 1598 1611 hyperglycemia hyperglycemia NN 1611 1612 , , , 1613 1623 suppresses suppress VBZ 1624 1631 insulin insulin NN 1632 1636 gene gene NN 1637 1650 transcription transcription NN 1651 1654 and and CC 1655 1659 thus thus RB 1660 1663 can can MD 1664 1671 explain explain VB 1672 1676 part part NN 1677 1679 of of IN 1680 1683 the the DT 1684 1688 beta beta NN 1689 1693 cell cell NN 1694 1701 glucose glucose NN 1702 1710 toxicity toxicity NN 1710 1711 . . .