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| 1 | Down-regulation of pancreatic transcription factors and incretin receptors in type 2 diabetes显示文摘Type 2 diabetes is one of the most prevalent and serious metabolic diseases.Under diabetic conditions,chronic hyperglycemia and subsequent induction of oxidative stress deteriorate pancreaticβ-cell function,which leads to the aggravation of type 2 diabetes.Although such phenomena are well known as glucose toxicity,its molecular mechanism remains unclear.In this review article,we describe the possible molecular mechanism forβ-cell dysfunction found in type 2 diabetes,focusing on(1)oxidative stress,(2)pancreatic transcription factors(PDX-1 and MafA)and(3)incretin receptors(GLP-1 and GIP receptors).Under such conditions,nuclear expression levels of PDX-1 and MafA are decreased,which leads to suppression of insulin biosynthesis and secretion.In addition,expression levels of GLP-1 and GIP receptors are decreased,which likely contributes to the impaired incretin effects found in diabetes.Taken together,it is likely that downregulation of pancreatic transcription factors(PDX-1and MafA)and down-regulation of incretin receptors(GLP-1 and GIP receptors)explain,at least in part,the molecular mechanism forβ-cell dysfunction found in type 2 diabetes. | Hideaki Kaneto Taka-aki Matsuoka | 2013 | World Journal of Diabetes2013，4，6： | 9 |
| 2 | Cancer detection by ubiquitin carboxyl-terminal esterase L1 methylation in pancreatobiliary fluids显示文摘AIM:To evaluate the utility of measuring epigenetic alterations in pancreatic and biliary fluids in determining molecular markers for pancreatobiliary cancers.METHODS:DNA was extracted from undiluted pancreatic and biliary fluids.As a surrogate for a genomewide hypomethylation assay,levels of long interspersed nuclear element-1(LINE-1) methylation were analyzed using bisulfite pyrosequencing.CpG island hypermethylation of 10 tumor-associated genes,aryl-hydrocarbon receptor repressor,adenomatous polyposis coli,calcium channel,voltage dependent,T type α1G subunit,insulin-like growth factor 2,O-6-methyl-guanine-DNA methyltransferase,neurogenin 1,CDKN2A,runt-related transcription factor 3(RUNX3),secreted frizzled-related protein 1,and ubiquitin carboxyl-terminal esterase L1(UCHL1),was analyzed using MethyLight.To examine the role of CpG methylation and histone deacetylation in the silencing of UCHL1,human gallbladder carcinoma cell lines and pancreatic carcinoma cell lines were treated with 2 or 5 μmol/L 5-AZA-dC for 72 h or 100 nmol/L Trichostatin A for 24 h.After the treatment,UCHL1 expression was analyzed by real-time reverse transcription-polymerase chain reaction.RESULTS:Pancreatobiliary cancers exhibited significantly lower LINE-1 methylation levels in pancreatic and biliary fluids than did noncancerous pancreatobiliary disease(58.7% ± 4.3% vs 61.7% ± 2.2%,P = 0.027;53.8% ± 6.6% vs 57.5% ± 1.7%,P = 0.007);however,LINE-1 hypomethylation was more evident in pancreatic cancer tissues than in pancreatic fluids(45.4% ± 5.5% vs 58.7% ± 4.3%,P < 0.001).CpG island hypermethylation of tumor-associated genes was detected at various frequencies,but it was not correlated with LINE-1 hypomethylation.Hypermethylation of the UCHL1 gene was cancer-specific and most frequently detected in pancreatic(67%) or biliary(70%) fluids from patients with pancreatobiliary cancer.As a single marker,hypermethylation of the UCHL1 gene in pancreatic and biliary fluids was most useful for the detection of pancreatic and pancreatobiliary cancers,respectively(100% specificity).Hypermethylation of the UCHL1 and RUNX3 genes in pancreatic and biliary fluids was the most useful combined marker for pancreatic(87% sensitivity and 100% specificity) and pancreatobiliary(97% sensitivity and 100% specificity) cancers.Treatment with a demethylating agent,5-AZA-2'-deoxycytidine,restored UCHL1 expression in pancreatobiliary cancer cell lines.CONCLUSION:Our results suggest that hypermethylation of UCHL1 and RUNX3 in pancreatobiliary fluid might be useful for the diagnosis of pancreatobiliary cancers. | Norihiro Kato Hiroyuki Yamamoto Yasushi Adachi Hirokazu Ohashi Hiroaki Taniguchi Hiromu Suzuki Mayumi Nakazawa Hiroyuki Kaneto Shigeru Sasaki Kohzoh Imai Yasuhisa Shinomura | 2013 | World Journal of Gastroenterology2013，19，11： | 3 |
| 3 | Factors affecting membrane-controlled drug release for an osmotic pump tablet (OPT) utilizing (SBE) 7 m -β-CD as both a solubilizer and osmotic agent显示文摘 | Kazuto Okimoto Atsuo Ohike Rinta Ibuki Osamu Aoki Norio Ohnishi Roger A. Rajewski Valentino J. Stella Tetsumi Irie Kaneto Uekama | 1999 | Journal of Controlled Release1999，，2： | 2 |
| 4 | Plasma pentraxin 3 levels are associated with carotid IMT in type 1 diabetic patients显示文摘 | Naoto Katakami Hideaki Kaneto Fumie Sakamoto | 2013 | Diabetes Research and Clinical Practice2013，99，2： | 1 |
| 5 | Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity 显示文摘 | Kaneto H Kajimoto Y Miyagawa J | 1999 | Diabetes1999，48，12： | 1 |
| 6 | 13 cell adapta- tion and decompensation during the progression of diabetes 显示文摘 | WEIR GC LAYBUTT DR KANETO H | 2001 | Diabetes2001，50，1： | 1 |
| 7 | Aldose reductase C-106T gene polymorphism is associated with diabetic retinopathy in Japanese patients with type 2 diabetes显示文摘 | Katakami N Kaneto H Takahara M | | 0，，03： | 1 |
| 8 | Involvement of oxidative stress in the pathogenesis of diabetes 显示文摘 | Kaneto H Katakami N Kawamori D | 2007 | Antioxid Redox Signal2007，9，3： | 1 |
| 9 | Involvement of oxidative stress in the pathogenesis of diabetes显示文摘 | Kaneto H Katakami N Kawamori D | 2007 | Antioxid Redox Sign Al2007，9，： | 1 |
| 10 | Increased expression of TGF-β1 mRNA in the obstructed kidney of rats with unilateral ureteral ligation显示文摘 | Morrissey J Klahr S | 1993 | Kidney Int1993，44，1： | 1 |
| 11 | Activation of the hexosamine pathway leads to deterioration of pancreatic: β-cell function through the induction of oxidative stress 显示文摘 | Kaneto H Xu G Song KH | 2001 | J Biol Chem2001，276，31： | 1 |
| 12 | Increased expression of TGF-β1 mRNA in the obstructed kidney of rats with unilateral ureteral ligation显示文摘 | KANETO H MORRISSEY J KLAHR S | 1993 | Kidney Int1993，44，4： | 1 |
| 13 | Activation of the Hexosamine Pathway Leads to Deterioration of Pancreatic β-Cell Function through the Induction of Oxidative Stress 显示文摘 | Kaneto H Xu G Song KH | 2001 | J Biol Chem2001，276，31： | 1 |
| 14 | Role of reactive oxygen species in the progression of type 2 diabetes and atherosclerosis显示文摘 | Kaneto H Katakami N Matsuhisa M | | 0，，： | 1 |
| 15 | PDX-1and MafA play a crucial role in pancreatic (3-celldifferentiation and maintenance of mature p-cell function 显示文摘 | KANETO H MIYATSUKA T KAWAMOHI D | 2008 | EndocrJ2008，55，2： | 1 |
| 16 | Serum endogenous secretory RAGE levels are inversely associated with carotid IMT in type 2 diabetic patients显示文摘 | Katakami N Matsuhisa M Kaneto H | 2007 | Atherosclerosis2007，190，1： | 1 |
| 17 | The forkhead transcription factor Foxol bridges the JNK pathway and the transcription factor PDX-1 through its intracetlular translocation 显示文摘 | KAWAMORI D KANETO H NAKATANI Y | 2006 | J Biol Chem2006，281，2： | 1 |
| 18 | The expression of Mrna for tumor necrosis factorα increases in the obstructed kidney of rat soon after unilateral ureteral ligation显示文摘 | Kaneto H Morrissey JJ McCracken R | 1996 | Nephrology1996，2，： | 1 |
| 19 | Increased expression of antioxidant and antiapoptotic genes in islets that may contribute to beta-cell survival during chronic hyperglycemia显示文摘 | Laybutt DR Kaneto H Hasenkamp W | 2002 | Diabetes2002，51，2： | 1 |
| 20 | Involvement of oxidative stress in the pathogenesis of diabetes 显示文摘 | Kaneto H Katakami N Kawamori D | 2007 | Antioxid Redox Signal2007，9，3： | 1 |
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