Kisspeptin stimulation of insulin secretion: mechanisms of action in mouse islets and rats.

Autor: Bowe JE; Division of Reproduction and Endocrinology, School of Biomedical and Health Sciences, King's College London, London, UK. james.bowe@kcl.ac.uk, King AJ, Kinsey-Jones JS, Foot VL, Li XF, O'Byrne KT, Persaud SJ, Jones PM
Jazyk: angličtina
Zdroj: Diabetologia [Diabetologia] 2009 May; Vol. 52 (5), pp. 855-62. Date of Electronic Publication: 2009 Feb 17.
DOI: 10.1007/s00125-009-1283-1
Abstrakt: Aims/hypothesis: Kisspeptin is a novel peptide identified as an endogenous ligand of the G-protein-coupled receptor 54 (GPR-54), which plays a crucial role in puberty and reproductive function. High levels of GPR-54 and kisspeptin have been reported in the pancreas and we have previously shown that kisspeptin potentiates glucose-induced insulin release from isolated islets, although the mechanisms underlying this effect were unclear.
Methods: Insulin secretion from isolated mouse islets was measured to characterise the effects of kisspeptin. The effects of kisspeptin on both p42/44 mitogen-activated protein kinase (MAPK) phosphorylation and intracellular Ca(2+)([Ca(2+)](i)) in mouse islets were also investigated. Furthermore, kisspeptin was administered to rats in vivo and effects on plasma insulin levels measured.
Results: In the current study, kisspeptin induced a concentration-dependent potentiation of glucose-induced (20 mmol/l) insulin secretion from mouse islets, with maximal effects at 1 micromol/l, but had no effect on insulin secretion at a substimulatory concentration of glucose (2 mmol/l). Activation of GPR-54 by kisspeptin also caused reversible increases in [Ca(2+)](i) in Fura-2 loaded dispersed islet cells. The kisspeptin-induced potentiation of glucose-induced insulin secretion was completely abolished by inhibitors of phospholipase C and p42/44 MAPK, but not by inhibitors of protein kinase C or p38 MAPK. Intravenous administration of kisspeptin into conscious, unrestrained rats caused an increase in circulating insulin levels, whilst central administration of kisspeptin had no effect, indicating a peripheral site of action.
Conclusions/interpretation: These observations suggest that neither typical protein kinase C isoforms nor p38 MAPK are involved in the potentiation of glucose-induced insulin release by kisspeptin, but intracellular signalling pathways involving phospholipase C, p42/44 MAPK and increased [Ca(2+)](i) are required for the stimulatory effects on insulin secretion. The observation that kisspeptin is also capable of stimulating insulin release in vivo supports the conclusion that kisspeptin is a regulator of beta cell function.
Databáze: MEDLINE
Externí odkaz: