AN INHIBITORY ROLE FOR PHOSPHATIDYLINOSITOL 3-KINASE IN INSULIN-SECRETION FROM PANCREATIC B-CELL LINE MIN6

被引:42
作者
HAGIWARA, S
SAKURAI, T
TASHIRO, F
HASHIMOTO, Y
MATSUDA, Y
NONOMURA, Y
MIYAZAKI, J
机构
[1] UNIV TOKYO,FAC MED,DEPT DIS RELATED GENE REGULAT RES SANDOZ,TOKYO 113,JAPAN
[2] UNIV TOKYO,FAC MED,DEPT PHARMACOL 1,TOKYO 113,JAPAN
[3] UNIV TOKYO,FAC MED,DEPT INTERNAL MED 1,TOKYO 113,JAPAN
[4] KYOWA HAKKO KOGYO CO LTD,TOKYO RES LABS,TOKYO 194,JAPAN
关键词
D O I
10.1006/bbrc.1995.2255
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Phosphatidylinositol 3-kinase (PI3-kinase) has been implicated in the regulation of vesicular transport. We examined the roles of PI3-kinase in the glucose-induced insulin secretion from the pancreatic beta cell line MIN6 by using wortmannin, a potent inhibitor of PI3-kinase. Low concentrations of wortmannin markedly potentiated the glucose-induced insulin secretion. This effect was probably mediated by PI3-kinase inhibition. Furthermore, wortmannin completely canceled the suppressive effect of insulin-like growth factor-I on insulin secretion from MIN6 cells. On the basis of these results, we discuss a possible role of PI3-kinase in the negative feed-back regulation of insulin secretion. (C) 1995 Academic Press, Inc.
引用
收藏
页码:51 / 59
页数:9
相关论文
共 19 条
[1]   WORTMANNIN IS A POTENT PHOSPHATIDYLINOSITOL 3-KINASE INHIBITOR - THE ROLE OF PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE IN NEUTROPHIL RESPONSES [J].
ARCARO, A ;
WYMANN, MP .
BIOCHEMICAL JOURNAL, 1993, 296 :297-301
[2]  
DAMEN JE, 1993, BLOOD, V81, P3204
[3]  
HURST RD, 1989, BIOCHEM SOC T, V17, P1086
[4]   DISRUPTION OF PDGF RECEPTOR TRAFFICKING BY MUTATION OF ITS PI-3 KINASE BINDING-SITES [J].
JOLY, M ;
KAZLAUSKAS, A ;
FAY, FS ;
CORVERA, S .
SCIENCE, 1994, 263 (5147) :684-687
[5]   INSULIN-STIMULATED GLUT4 TRANSLOCATION IS RELEVANT TO THE PHOSPHORYLATION OF IRS-1 AND THE ACTIVITY OF PI3-KINASE [J].
KANAI, F ;
ITO, K ;
TODAKA, M ;
HAYASHI, H ;
KAMOHARA, S ;
ISHII, K ;
OKADA, T ;
HAZEKI, O ;
UI, M ;
EBINA, Y .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 195 (02) :762-768
[6]   COMMON ELEMENTS IN GROWTH-FACTOR STIMULATION AND ONCOGENIC TRANSFORMATION - 85-KD PHOSPHOPROTEIN AND PHOSPHATIDYLINOSITOL KINASE-ACTIVITY [J].
KAPLAN, DR ;
WHITMAN, M ;
SCHAFFHAUSEN, B ;
PALLAS, DC ;
WHITE, M ;
CANTLEY, L ;
ROBERTS, TM .
CELL, 1987, 50 (07) :1021-1029
[7]   ESTABLISHMENT OF A PANCREATIC BETA-CELL LINE THAT RETAINS GLUCOSE-INDUCIBLE INSULIN-SECRETION - SPECIAL REFERENCE TO EXPRESSION OF GLUCOSE TRANSPORTER ISOFORMS [J].
MIYAZAKI, JI ;
ARAKI, K ;
YAMATO, E ;
IKEGAMI, H ;
ASANO, T ;
SHIBASAKI, Y ;
OKA, Y ;
YAMAMURA, KI .
ENDOCRINOLOGY, 1990, 127 (01) :126-132
[8]   IRS-1 IS A COMMON ELEMENT IN INSULIN AND INSULIN-LIKE GROWTH FACTOR-I SIGNALING TO THE PHOSPHATIDYLINOSITOL 3'-KINASE [J].
MYERS, MG ;
SUN, XJ ;
CHEATHAM, B ;
JACHNA, BR ;
GLASHEEN, EM ;
BACKER, JM ;
WHITE, MF .
ENDOCRINOLOGY, 1993, 132 (04) :1421-1430
[9]  
NAKANISHI S, 1992, J BIOL CHEM, V267, P2157
[10]   CHARACTERIZATION OF 2 85KD PROTEINS THAT ASSOCIATE WITH RECEPTOR TYROSINE KINASES, MIDDLE-T/PP60C-SRC COMPLEXES, AND PI3-KINASE [J].
OTSU, M ;
HILES, I ;
GOUT, I ;
FRY, MJ ;
RUIZLARREA, F ;
PANAYOTOU, G ;
THOMPSON, A ;
DHAND, R ;
HSUAN, J ;
TOTTY, N ;
SMITH, AD ;
MORGAN, SJ ;
COURTNEIDGE, SA ;
PARKER, PJ ;
WATERFIELD, MD .
CELL, 1991, 65 (01) :91-104