Expression of peroxisome proliferator-activated receptor γ (PPARγ) in normal human pancreatic islet cells

被引:178
作者
Dubois, M
Pattou, F
Kerr-Conte, J
Gmyr, V
Vandewalle, B
Desreumaux, P
Auwerx, J
Schoonjans, K
Lefebvre, J
机构
[1] ULP, CNRS, INSERM, IGBMC, F-67404 Illkirch, France
[2] Univ Hosp Ctr Lille, Res Lab Inflammatory Intestinal Disorders CRI4U00, Lille, France
[3] Univ Hosp Ctr Lille, UPRES 1048, Lille, France
关键词
Type II diabetes; peroxisome proliferator-activated receptor gamma; human pancreas; islets; beta cell; thiazolidinediones; troglitazone; rosiglitazone;
D O I
10.1007/s001250051508
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims/hypothesis. Thiazolidinediones are reported to improve pancreatic islet morphology and beta-cell function in rodents, supporting the hypothesis of a direct action of thiazolidinediones on endocrine islet cells. In this study we examined the expression of the peroxisome proliferator-activated receptor gamma, a nuclear receptor that is activated by naturally occurring fatty acids and synthetic thiazolidinediones, in normal human endocrine pancreatic cells. Methods. Human islets were isolated from pancreata harvested in ten brain-dead lean non-diabetic adult donors. We analysed the gene and protein expression of the human peroxisome proliferator-activated receptor gamma and evaluated the effects of peroxisome proliferator-activated receptor gamma agonist on insulin secretion in human islet preparations, Results. The RT-PCR carried out on total RNA from four distinct human islet preparations demonstrated the presence of peroxisome proliferator-activated receptor gamma mRNA. Western blot analysis showed the consistent expression of peroxisome proliferator-activated receptor gamma protein. Peroxisome proliferator-activated receptor gamma was shown to be present in all three endocrine cell types studied (alpha, beta and delta cells) by immunohistochemistry. Conclusion/interpretation. We found that peroxisome proliferator-activated receptor gamma is highly expressed in human islet endocrine cells, both at the mRNA and protein levels. These results support the hypothesis of a direct influence of peroxisome proliferator-activated receptor gamma agonist on human pancreatic endocrine cells.
引用
收藏
页码:1165 / 1169
页数:5
相关论文
共 10 条
[1]   PPARγ, the ultimate thrifty gene [J].
Auwerx, J .
DIABETOLOGIA, 1999, 42 (09) :1033-1049
[2]   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
[3]   Peroxisome proliferator-activated receptor-γ agonist, rosiglitazone, protects against nephropathy and pancreatic islet abnormalities in Zucker fatty rats [J].
Buckingham, RE ;
Al-Barazanji, KA ;
Toseland, CDN ;
Slaughter, M ;
Connor, SC ;
West, A ;
Bond, B ;
Turner, NC ;
Clapham, JC .
DIABETES, 1998, 47 (08) :1326-1334
[4]   Treatment with the oral antidiabetic agent troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance [J].
Cavaghan, MK ;
Ehrmann, DA ;
Byrne, MM ;
Polonsky, KS .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (03) :530-537
[5]   Inflammatory alterations in mesenteric adipose tissue in Crohn's disease [J].
Desreumaux, P ;
Ernst, O ;
Geboes, K ;
Gambiez, L ;
Berrebi, D ;
Müller-Alouf, H ;
Hafraoui, S ;
Emilie, D ;
Ectors, N ;
Peuchmaur, M ;
Cortot, A ;
Capron, M ;
Auwerx, J ;
Colombel, JF .
GASTROENTEROLOGY, 1999, 117 (01) :73-81
[6]   Peroxisome proliferator-activated receptors: Nuclear control of metabolism [J].
Desvergne, B ;
Wahli, W .
ENDOCRINE REVIEWS, 1999, 20 (05) :649-688
[7]   The organization, promoter analysis, and expression of the human PPAR gamma gene [J].
Fajas, L ;
Auboeuf, D ;
Raspe, E ;
Schoonjans, K ;
Lefebvre, AM ;
Saladin, R ;
Najib, J ;
Laville, M ;
Fruchart, JC ;
Deeb, S ;
VidalPuig, A ;
Flier, J ;
Briggs, MR ;
Staels, B ;
Vidal, H ;
Auwerx, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (30) :18779-18789
[8]   Effect of troglitazone on B cell function, insulin sensitivity, and glycemic control in subjects with type 2 diabetes mellitus [J].
Prigeon, RL ;
Kahn, SE ;
Porte, D .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (03) :819-823
[9]   Troglitazone lowers islet fat and restores beta cell function of Zucker diabetic fatty rats [J].
Shimabukuro, M ;
Zhou, YT ;
Lee, Y ;
Unger, RH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (06) :3547-3550
[10]   Human pancreatic islet quality control: Easy assessment of metabolic functions [J].
Vandewalle, B ;
Douillard, C ;
Conte, JK ;
Gmyr, V ;
Riachi, R ;
D'herbomez, M ;
Pattou, F ;
Lefebvre, J .
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES, 1999, 107 (03) :214-219