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- Title
Regulation of β-Cell Function by Kisspeptin.
- Authors
Persaud, Shanta J.; Bowe, James; King, Aileen; Jones, Peter M.
- Abstract
Kisspeptin (KP) is a novel peptide encoded by the Kiss-1 gene. Recent experiments using fasted animals have suggested that KP plays an important role as a whole body energy sensor, acting to modify fertility and puberty by relaying information on nutritional status to the GnRH-gonadotrophin axis. In addition, KP and its receptor (GPR54) are expressed abundantly in pancreas and placenta, organs known to be involved in fuel sensing. We have recently identified KP and GPR54 in islets and we have now quantified KP and GPR54 mRNA levels in islets isolated from ob/ob, lean and pregnant mice to determine whether islet KP or GPR54 levels are altered in different metabolic states. KP mRNA levels were reduced by 30.1±6.5% (P<0.01, n=6) in ob/ob mouse islets compared to lean controls, whilst there was no significant difference in GPR54 mRNA levels. Similar reductions (27.8±14.6%) in KP mRNA levels were observed in islets isolated from pregnant mice. KP (62.5nM-1µM) induced a concentration-dependent potentiation of glucose-induced insulin secretion from isolated mouse islets (20mM glucose: 1.31±0.27 ng/islet/h; + lµM KP: 2.50±-0.26, n=9, P<0.001), but it did not initiate insulin secretion at 2mM glucose (104.8±31.4% basal, n=9, P>0.2). The stimulatory effect of KP on insulin secretion was significantly (P<0.001) inhibited by inhibition of the mitogen activated protein kinase cascade, but not by inhibition of the p38 kinase pathway (20mM glucose + 100nM kisspeptin: 2.58±0.15 ng/islet/h; +50µM PD98059: 0.65±0.08; + 50µM SB203580:3.251±0.62 n=8-9). These observations implicate a role for the KP/GPR54 system in the regulation of islet function that may be important in metabolic states such as obesity and pregnancy.
- Subjects
PEPTIDES; CELLULAR control mechanisms; PANCREATIC beta cells; ISLANDS of Langerhans; MESSENGER RNA; LUTEINIZING hormone releasing hormone; INSULIN; LABORATORY mice
- Publication
Diabetes, 2007, Vol 56, pA438
- ISSN
0012-1797
- Publication type
Article