The Mechanism of Inhibition of Insulin Secretion by Ghrelin

Ghrelin具有多种作用，包括分泌生长激素或刺激食欲等。Ghrelin还具有抑制胰岛素分泌的作用。我们已经报道ghrelin可以通过诱导IA-2 β抑制胰岛素分泌（Doi A.等人PNAS 103：885，2006）。在该研究中，除了IA-2 β，还鉴定了AMPK/UCP 2途径参与该生长素释放肽对胰岛素分泌抑制的作用（Wang Y等，FEBS Lett 584：1503，2010）。由于UCP 2具有抗氧化应激的保护作用，因此研究了ghrelin对细胞增殖和凋亡的抗氧化应激的保护作用，并且ghrelin剂量依赖性地改善了由H2 O2诱导的MIN 6细胞的细胞增殖降低和细胞凋亡增加。然而，出乎意料的是，这种ghrelin的作用不是通过AMPK-UCP 2途径，而是通过MAPK和PI 3 K途径。因此，ghrelin对β细胞和葡萄糖代谢具有复杂的作用。Ghrelin确实抑制胰岛素分泌，不利于葡萄糖代谢，然而，Ghrelin也显示出对氧化应激的保护作用，有利于葡萄糖代谢。这些ghrelin对β细胞的影响的进一步澄清将是必要的。

Ghrelin has been reported to show various effects including the secretion of growth hormone or the stimulation of appetite etc. Ghrelin has also been reported to inhibit insulin secretion. We have reported that ghrelin could inhibit insulin secretion via induction of IA-2beta (Doi A. et al. PNAS 103:885,2006). In this study, other than IA-2beta, involvement of AMPK/UCP2 pathway in this ghrelin’s effects on the inhibition of insulin secretion was identified (Wang Y et al. FEBS Lett 584:1503,2010). Since UCP2 has protective effects against oxidative stress, the protective effects of ghrelin on cell proliferation and apoptosis against oxidative stress were investigated, and ghrelin, dose-dependently, ameliorated decreased cell proliferation and increased apoptosis induced by H2O2 in MIN6 cells. However, unexpectedly, this ghrelin’s effects was not via AMPK-UCP2 pathway, but MAPK and PI3K pathways. Therefore, ghrelin has complicated effects on beta cells and glucose metabolism. Ghrelin does inhibit insulin secretion, bad for glucose metabolism, however, ghrelin also showed protective effects against oxidative stress, good for glucose metabolism. Further clarification of these ghrelin’s effects on beta cells will be necessar y.