The Mechanism of Inhibition of Insulin Secretion by Ghrelin

据报道，胃饥饿素具有多种作用，包括分泌生长激素或刺激食欲等。据报道，胃饥饿素也能抑制胰岛素分泌。我们报道过饥饿素可以通过诱导ia -2 β抑制胰岛素分泌（Doi A.等）。PNAS 103:885, 2006)。本研究发现除了ia -2 β外，AMPK/UCP2通路还参与了该ghrelin抑制胰岛素分泌的作用（Wang Y等）。FEBS Lett 584:1503,2010)。由于UCP2对氧化应激具有保护作用，我们研究了ghrelin对氧化应激细胞增殖和凋亡的保护作用，发现ghrelin以剂量依赖的方式改善H2O2诱导MIN6细胞增殖下降和凋亡增加的情况。然而，出乎意料的是，这种ghrelin的作用不是通过AMPK-UCP2途径，而是通过MAPK和PI3K途径。因此，ghrelin对β细胞和葡萄糖代谢具有复杂的影响。Ghrelin抑制胰岛素分泌，不利于葡萄糖代谢，但对氧化应激也有保护作用，有利于葡萄糖代谢。进一步阐明这些生长素对β细胞的影响是必要的。

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.