抄録
Ghrelin is a new peptide, purified from the stomach as an endogenous ligand for growth-hormone secretagogue receptor (GHS-R). Ghrelin stimulates growth-hormone release and food intake and is thought to play a central role in the energy metabolism. Ghrelin and GHS-R are present in the pancreatic islets. This study was aimed at examining the effects and action mechanisms of ghrelin on Ca2+ signaling and insulin release in islet β-cells. Cytosolic free Ca2+ concentration ([Ca2+]i) was measured in rat β-cells with fura-2 microfluorometry. Single β-cells were isolated from the rat pancreas and incubated with 1 mM fura-2/AM for 30 min at 37°C in KRB containing 2.8 mM glucose. Fluorescent images due to 340 and 380 nm were detected every 5 sec, and the ratio image was produced by an Argus-50 system. Ratio value was converted to [Ca2+]i with calibration curves. Insulin release experiments were performed in islets under static incubation conditions and insulin was determined using EIA kit. Ghrelin at 10−8 M suppressed increases in [Ca2+]i induced by 8.3 mM glucose and those by pituitary adenylate cyclase-activating polypeptide (PACAP) (10−9 M) at 8.3 mM glucose in single β-cells. Ghrelin also suppressed the [Ca2+]i increases by forskolin, a cAMP increasing agent, but not those by 10−5 M Ach in single β-cells. Insulin release in response to 8.3 mM glucose was inhibited by ghrelin. The results indicate that ghrelin counteracts Ca2+ signaling evoked by glucose and PACAP-cAMP pathway in islet β-cells, which is linked to inhibition of insulin release. [Jpn J Physiol 54 Suppl:S74 (2004)]
