Ghrelin is present in pancreatic α-cells of humans and rats and stimulates insulin secretion

被引:491
作者
Date, Y
Nakazato, M [1 ]
Hashiguchi, S
Dezaki, K
Mondal, MS
Hosoda, H
Kojima, M
Kangawa, K
Arima, T
Matsuo, H
Yada, T
Matsukura, S
机构
[1] Miyazaki Med Coll, Dept Internal Med 3, Miyazaki 8891692, Japan
[2] Natl Cardiovasc Ctr, Res Inst, Osaka, Japan
[3] Jichi Med Sch, Dept Physiol, Minami Kawachi, Tochigi 32904, Japan
[4] Kagoshima Univ, Fac Med, Dept Internal Med 2, Kagoshima 890, Japan
关键词
D O I
10.2337/diabetes.51.1.124
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Ghrelin, a novel growth hormone-releasing peptide isolated from human and rat stomach, is a 28-amino acid peptide with a posttranslational acylation modification that is indispensable for stimulating growth hormone secretion by increasing intracellular Ca2+ concentration. It also functions in the regulation of feeding behavior, energy metabolism, and gastric acid secretion and motility. Using two different antibodies against the NH2- and COOH-terminal regions of ghrelin, we studied its localization in human and rat pancreas by immunohistochemistry. Ghrelin-immunoreactive cells were identified at the periphery of pancreatic islets in both species. Ghrelin co-localized exclusively with glucagon in rat islets, indicating that it is produced in alpha-cells. We identified ghrelin and des-acyl ghrelin in the rat pancreas using reverse-phase high-performance liquid chromatography combined with two radioimmunoassays. We also detected mRNA encoding ghrelin and its receptor in the rat pancreatic islets. Ghrelin increased the cytosolic free Ca2+ concentration in beta-cells and stimulated insulin secretion when it was added to isolated rat pancreatic islets. These findings indicate that ghrelin may regulate islet function in an endocrine and/or paracrine manner.
引用
收藏
页码:124 / 129
页数:6
相关论文
共 28 条
[1]   ON THE INVITRO AND INVIVO ACTIVITY OF A NEW SYNTHETIC HEXAPEPTIDE THAT ACTS ON THE PITUITARY TO SPECIFICALLY RELEASE GROWTH-HORMONE [J].
BOWERS, CY ;
MOMANY, FA ;
REYNOLDS, GA ;
HONG, A .
ENDOCRINOLOGY, 1984, 114 (05) :1537-1545
[2]  
CAPELLA C, 1978, CELL TISSUE RES, V186, P25
[3]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[4]   INCRETIN CONCEPT TODAY [J].
CREUTZFELDT, W .
DIABETOLOGIA, 1979, 16 (02) :75-85
[5]   Central effects of a novel acylated peptide, ghrelin, on growth hormone release in rats [J].
Date, Y ;
Murakami, N ;
Kojima, M ;
Kuroiwa, T ;
Matsukura, S ;
Kangawa, K ;
Nakazato, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 275 (02) :477-480
[6]   Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans [J].
Date, Y ;
Kojima, M ;
Hosoda, H ;
Sawaguchi, A ;
Mondal, MS ;
Suganuma, T ;
Matsukura, S ;
Kangawa, K ;
Nakazato, M .
ENDOCRINOLOGY, 2000, 141 (11) :4255-4261
[7]   Ghrelin acts in the central nervous system to stimulate gastric acid secretion [J].
Date, Y ;
Nakazato, M ;
Murakami, N ;
Kojima, M ;
Kangawa, K ;
Matsukura, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 280 (03) :904-907
[8]   A-like cells in the rat stomach contain ghrelin and do not operate under gastrin control [J].
de la Cour, CD ;
Björkqvist, M ;
Sandvik, AK ;
Bakke, I ;
Zhao, CM ;
Chen, D ;
Håkanson, R .
REGULATORY PEPTIDES, 2001, 99 (2-3) :141-150
[9]  
Freychet P., 1990, HORMONES MOL DIS, P489
[10]  
HAKANSON R, 1984, EVOLUTION TUMOUR PAT, P371