PANCREATIC BETA-CELL REPLICATION AND AMELIORATION OF SURGICAL DIABETES BY REG PROTEIN

被引:229
作者
WATANABE, T
YONEMURA, Y
YONEKURA, H
SUZUKI, Y
MIYASHITA, H
SUGIYAMA, K
MORIIZUMI, S
UNNO, M
TANAKA, O
KONDO, H
BONE, AJ
TAKASAWA, S
OKAMOTO, H
机构
[1] TOHOKU UNIV, SCH MED, DEPT BIOCHEM, AOBA KU, SENDAI, MIYAGI 980, JAPAN
[2] TOHOKU UNIV, SCH MED, DEPT ANAT, AOBA KU, SENDAI, MIYAGI 980, JAPAN
[3] KANAZAWA UNIV, SCH MED, DEPT SURG, KANAZAWA, ISHIKAWA 920, JAPAN
[4] UNIV BRIGHTON, DEPT PHARM, BRIGHTON BN2 4GJ, E SUSSEX, ENGLAND
关键词
REG GENE; DIABETES MELLITUS; ISLETS OF LANGERHANS; GROWTH FACTOR;
D O I
10.1073/pnas.91.9.3589
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We previously isolated from a rat regenerating islet cDNA library a gene named Reg, which is expressed in regenerating islets but is not expressed in normal islets. Here we examined the effect of rat Reg protein on pancreatic beta-cell replication using both 90% depancreatized rats and isolated islets. The depancreatized rats that received i.p. administration of recombinant rat Reg protein (1 mg/kg per day) for 2 months showed amelioration of the surgical diabetes, as evidenced by a significant decrease in blood glucose with an increased beta cell mass in the residual pancreas, In isolated rat islets, Reg protein (18-180 nM: 0.3-3 mu g/ml) significantly increased [H-3]thymidine incorporation into the nuclei of beta cells. These results indicate that Reg protein is a growth factor for pancreatic beta cells and also suggest that the administration of Reg protein could be used as another therapeutic approach for diabetes mellitus.
引用
收藏
页码:3589 / 3592
页数:4
相关论文
共 21 条
[1]   N-TERMINAL SEQUENCE EXTENSION IN THE GLYCOSYLATED FORMS OF HUMAN PANCREATIC STONE PROTEIN - THE 5-OXOPROLINE N-TERMINAL CHAIN IS O-GLYCOSYLATED ON THE 5TH AMINO-ACID RESIDUE [J].
DECARO, AM ;
ADRICH, Z ;
FOURNET, B ;
CAPON, C ;
BONICEL, JJ ;
DECARO, JD ;
ROVERY, M .
BIOCHIMICA ET BIOPHYSICA ACTA, 1989, 994 (03) :281-284
[2]  
DECARO AM, 1987, EUR J BIOCHEM, V168, P201
[3]   EXPRESSION OF AN ISLET REGENERATING (REG) GENE IN ISOLATED RAT ISLETS - EFFECTS OF NUTRIENT AND NONNUTRIENT GROWTH-FACTORS [J].
FRANCIS, PJ ;
SOUTHGATE, JL ;
WILKIN, TJ ;
BONE, AJ .
DIABETOLOGIA, 1992, 35 (03) :238-242
[4]   ISOLATION, CHARACTERIZATION, AND DISTRIBUTION OF AN UNUSUAL PANCREATIC HUMAN SECRETORY PROTEIN [J].
GROSS, J ;
CARLSON, RI ;
BRAUER, AW ;
MARGOLIES, MN ;
WARSHAW, AL ;
WANDS, JR .
JOURNAL OF CLINICAL INVESTIGATION, 1985, 76 (06) :2115-2126
[5]  
HELLERSTROM C, 1976, ACTA ENDOCRINOL-COP, V83, P145
[6]   APPEARANCE OF A REGENERATING (REG) GENE PROTEIN IN PANCREATIC-ISLETS OF REMISSION BB WOR TKY RATS [J].
ISHII, C ;
KAWAZU, S ;
TOMONO, S ;
OHNO, T ;
SHIMIZU, M ;
KATO, N ;
FUKUDA, M ;
ITO, Y ;
KURIHARA, S ;
MURATA, K ;
KOMEDA, K .
ENDOCRINE JOURNAL, 1993, 40 (02) :269-273
[7]   ISOLATION AND CHARACTERIZATION OF HUMAN REG PROTEIN PRODUCED IN SACCHAROMYCES-CEREVISIAE [J].
ITOH, T ;
TSUZUKI, H ;
KATOH, T ;
TERAOKA, H ;
MATSUMOTO, K ;
YOSHIDA, N ;
TERAZONO, K ;
WATANABE, T ;
YONEKURA, H ;
YAMAMOTO, H ;
OKAMOTO, H .
FEBS LETTERS, 1990, 272 (1-2) :85-88
[8]  
LOGOTHETOPOULOS J, 1972, ENDOCRINE PANCREAS E, V1, P67
[9]   EXPRESSION OF REG/PSP, A PANCREATIC EXOCRINE GENE - RELATIONSHIP TO CHANGES IN ISLET BETA-CELL MASS [J].
MIYAURA, C ;
CHEN, L ;
APPEL, M ;
ALAM, T ;
INMAN, L ;
HUGHES, SD ;
MILBURN, JL ;
UNGER, RH ;
NEWGARD, CB .
MOLECULAR ENDOCRINOLOGY, 1991, 5 (02) :226-234
[10]   ISOLATION, STRUCTURAL DETERMINATION AND EXPRESSION OF A NOVEL REG GENE, HUMAN REGI-BETA [J].
MORIIZUMI, S ;
WATANABE, T ;
UNNO, M ;
NAKAGAWARA, K ;
SUZUKI, Y ;
MIYASHITA, H ;
YONEKURA, H ;
OKAMOTO, H .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 1994, 1217 (02) :199-202