Inhibitory effect of kisspeptins on insulin secretion from isolated mouse islets

被引:48
作者
Vikman, J. [1 ]
Ahren, B. [1 ]
机构
[1] Lund Univ, Dept Clin Sci, Div Med, Biomed Ctr, SE-22184 Lund, Sweden
基金
瑞典研究理事会;
关键词
insulin secretion; islets; kisspeptin; PROTEIN-COUPLED RECEPTOR; GONADOTROPIN; KISS-1; RELEASE; GPR54;
D O I
10.1111/j.1463-1326.2009.01116.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Islet hormone secretion is regulated by a variety of factors, and many of these signal through G protein-coupled receptors (GPCRs). A novel islet GPCR is GPR54, which couples to the Gq isoform of G proteins, which in turn signal through the phospholipase C pathway. Ligands for GPR54 are kisspeptins, which are peptides encoded in the KISS1 gene and also expressed in islet beta-cells. The KISS1 gene encodes a hydrophobic 145-amino acid protein that is cleaved into a 54-amino acid protein, kisspeptin-54 or KP54. Shorter kisspeptins also exist, such as kisspeptin-10 (KP10) and kisspeptin-13 (KP13). The involvement of GPR54 and kisspeptins in the regulation of islet function is not known. To address this problem, we incubated isolated mouse islets in the presence of KP13 and KP54 for 60 min and measured insulin secretion. We found that both KP13 and KP54 at 10 nM, 100 nM and 1 mu M inhibited insulin secretion in the presence of 2.8 mM glucose. However, by increasing the glucose concentration, this inhibitory action of the kisspeptins vanished. Thus, at 11.1 mM glucose, KP13 and KP54 inhibited insulin secretion only at high doses, and at 16.7 mM they no longer inhibited insulin secretion in any of the doses. We conclude that kisspeptins inhibit insulin secretion at glucose concentrations below 11.1 mM. This suggests that kisspeptins are regulating insulin secretion at physiological concentrations of glucose. The mechanisms by which kisspeptins regulate islet function and insulin secretion are unknown and will be further investigated.
引用
收藏
页码:197 / 201
页数:5
相关论文
共 24 条
[1]   Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes [J].
Ahren, Bo .
NATURE REVIEWS DRUG DISCOVERY, 2009, 8 (05) :369-385
[2]   GLUCOSE INDUCES CLOSURE OF SINGLE POTASSIUM CHANNELS IN ISOLATED RAT PANCREATIC BETA-CELLS [J].
ASHCROFT, FM ;
HARRISON, DE ;
ASHCROFT, SJH .
NATURE, 1984, 312 (5993) :446-448
[3]   FMRFamide-related neuropeptides are agonists of the orphan G-protein-coupled receptor GPR54 [J].
Clements, MK ;
McDonald, TP ;
Wang, RP ;
Xie, GC ;
O'Dowd, BF ;
George, SR ;
Austin, CP ;
Liu, QY .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 284 (05) :1189-1193
[4]  
Colledge W. H., 2008, V46, P117, DOI 10.1007/400_2007_050
[5]   Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males [J].
Dhillo, WS ;
Chaudhri, OB ;
Patterson, M ;
Thompson, EL ;
Murphy, KG ;
Badman, MK ;
McGowan, BM ;
Amber, V ;
Patel, S ;
Ghatei, MA ;
Bloom, SR .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2005, 90 (12) :6609-6615
[6]   From KISS1 to kisspeptins: An historical perspective and suggested nomenclature [J].
Gottsch, Michelle L. ;
Clifton, Donald K. ;
Steiner, Robert A. .
PEPTIDES, 2009, 30 (01) :4-9
[7]   A role for kisspeptins in the regulation of gonadotropin secretion in the mouse [J].
Gottsch, ML ;
Cunningham, MJ ;
Smith, JT ;
Popa, SM ;
Acohido, BV ;
Crowley, WF ;
Seminara, S ;
Clifton, DK ;
Steiner, RA .
ENDOCRINOLOGY, 2004, 145 (09) :4073-4077
[8]   KISS1 metastasis suppression and emergent pathways [J].
Harms, JF ;
Welch, DR ;
Miele, ME .
CLINICAL & EXPERIMENTAL METASTASIS, 2003, 20 (01) :11-18
[9]   A role for kisspeptin in islet function [J].
Hauge-Evans, A. C. ;
Richardson, C. C. ;
Milne, H. M. ;
Christie, M. R. ;
Persaud, S. J. ;
Jones, P. M. .
DIABETOLOGIA, 2006, 49 (09) :2131-2135
[10]   Triggering and amplifying pathways of regulation of insulin secretion by glucose [J].
Henquin, JC .
DIABETES, 2000, 49 (11) :1751-1760