PPAR-γ overexpression suppresses glucose-induced proinsulin biosynthesis and insulin release synergistically with pioglitazone in MIN6 cells

被引:22
作者
Nakamichi, Y
Kikuta, T
Ito, E
Imaizumi-Ohara, M
Nishiwaki, C
Ishida, H
Nagamatsu, S
机构
[1] Kyorin Univ, Sch Med, Dept Biochem 2, Mitaka, Tokyo 1818611, Japan
[2] Kyorin Univ, Sch Med, Dept Internal Med 3, Mitaka, Tokyo 1818611, Japan
关键词
PPAR-gamma; proinsulin biosynthesis; insulin secretion; pioglitazone;
D O I
10.1016/S0006-291X(03)01045-3
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
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) regulates several cellular functions; however, its physiological role in pancreatic beta cell functions remains to be determined. In the present study, we investigated the synergistic effect of PPAR-gamma and its agonist, pioglitazone, on proinsulin biosynthesis and insulin release in a glucose-responsible insulinoma cell line, MIN6 cells. Expression of PPAR-gamma in MIN6 cells was not detectable by RT-PCR and immunoblot analysis. When PPAR-gamma-1 was overexpressed adenovirally in MIN6 cells, glucose-stimulated proinsulin biosynthesis and insulin release were inhibited. Pioglitazone treatment alone had no effects on these parameters of cell function in control MIN6 cells, although pioglitazone synergistically augmented the inhibitory effect of PPAR-gamma on proinsulin biosynthesis and insulin release under the condition of PPAR-gamma overexpression. Our results demonstrate that PPAR-gamma plays a negative role in pancreatic beta cells. (C) 2003 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:832 / 836
页数:5
相关论文
共 27 条
[1]   Reproducibility of targeted gene expression measurements in human islets of Langerhans [J].
Barry, R ;
Tadayyon, M ;
Green, IC .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 298 (03) :350-356
[2]   Thiazolidinediones produce a conformational change in peroxisomal proliferator-activated receptor-gamma: Binding and activation correlate with antidiabetic actions in db/db mice [J].
Berger, J ;
Bailey, P ;
Biswas, C ;
Cullinan, CA ;
Doebber, TW ;
Hayes, NS ;
Saperstein, R ;
Smith, RG ;
Leibowitz, MD .
ENDOCRINOLOGY, 1996, 137 (10) :4189-4195
[3]   Differential expression of peroxisome proliferator-activated receptors (PPARs): Tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat [J].
Braissant, O ;
Foufelle, F ;
Scotto, C ;
Dauca, M ;
Wahli, W .
ENDOCRINOLOGY, 1996, 137 (01) :354-366
[4]   Identification of the docked granule pool responsible for the first phase of glucose-stimulated insulin secretion [J].
Daniel, S ;
Noda, M ;
Straub, SG ;
Sharp, GWG .
DIABETES, 1999, 48 (09) :1686-1690
[5]   Expression of peroxisome proliferator-activated receptor γ (PPARγ) in normal human pancreatic islet cells [J].
Dubois, M ;
Pattou, F ;
Kerr-Conte, J ;
Gmyr, V ;
Vandewalle, B ;
Desreumaux, P ;
Auwerx, J ;
Schoonjans, K ;
Lefebvre, J .
DIABETOLOGIA, 2000, 43 (09) :1165-1169
[6]   β-cell mass dynamics in Zucker diabetic fatty rats -: Rosiglitazone prevents the rise in net cell death [J].
Finegood, DT ;
McArthur, MD ;
Kojwang, D ;
Thomas, MJ ;
Topp, BG ;
Leonard, T ;
Buckingham, RE .
DIABETES, 2001, 50 (05) :1021-1029
[7]   15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2) IS A LIGAND FOR THE ADIPOCYTE DETERMINATION FACTOR PPAR-GAMMA [J].
FORMAN, BM ;
TONTONOZ, P ;
CHEN, J ;
BRUN, RP ;
SPIEGELMAN, BM ;
EVANS, RM .
CELL, 1995, 83 (05) :803-812
[8]   CHARACTERIZATION OF NEW ORAL ANTIDIABETIC AGENT CS-045 - STUDIES IN KK AND OB OB MICE AND ZUCKER FATTY RATS [J].
FUJIWARA, T ;
YOSHIOKA, S ;
YOSHIOKA, T ;
USHIYAMA, I ;
HORIKOSHI, H .
DIABETES, 1988, 37 (11) :1549-1558
[9]   Acute inhibition of proinsulin biosynthesis at the translational level by palmitic acid [J].
Katahira, H ;
Nagamatsu, S ;
Ozawa, S ;
Nakamichi, Y ;
Yamaguchi, S ;
Furukawa, H ;
Takizawa, M ;
Yoshimoto, K ;
Itagaki, E ;
Ishida, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 282 (02) :507-510
[10]   Roles of PPARs in health and disease [J].
Kersten, S ;
Desvergne, B ;
Wahli, W .
NATURE, 2000, 405 (6785) :421-424