The identification and functional analysis of lipid- or amino acid- responsive genes in pancreatic beta cells

利用小鼠胰腺β细胞系βHC9细胞，我们首次证明了FATP(脂肪酸转运蛋白)的主要亚型是FATP4，没有发现新的ACBP(酰基辅酶A结合蛋白)亚型。然后，我们试图找出1 mM棕榈酸酯处理72小时后差异表达的基因，这导致葡萄糖诱导的胰岛素分泌增加。我们应用了两种综合的方法，即荧光差异显示(FDD；象形文字，Genmyx，Inc.)和DNA微阵列(GeneChip System，Affymetrix，Inc.)。尽管结果没有重叠，但我们总共获得了100多个脂质反应基因，其中包括新的基因。我们还确认了一例日本高胰岛素伴高氨血症(HI-HA综合征)病例，其原因是谷氨酸脱氢酶基因的一个激活突变。氨基酸代谢和葡萄糖动态平衡的相互作用引起了人们对病理生理学的极大兴趣。

Using mouse pancreatic beta cell line, beta HC9 cells, we first demonstrated that major isoform of FATP (fatty acid transport protein) expressed was FATP4, and no novel isoform was found for ACBP (acyl-CoA binding protein). We then tried to identify genes whose expression was differentially regulated by 1mM palmitate treatment for 72 hours which resulted in the enhanced glucose-induced insulin secretion. We applied two comprehensive methods, namely, fluorescent differential display (FDD ; HIEROGLYPH, GENOMYX, Inc) and DNA microarray (GeneChip system, Affymetrix, Inc). Although the results did not have an overlap, altogether we obtained more than 100 lipid-responsive genes, including novel ones. We also identified a Japanese case of hyperinsulinism with hyperammonemia (HI-HA syndrome) due to an activating mutation in the glutamate dehydrogenase gene. The pathophysiology was of great interest as the interplay of amino acid metabolism and glucose homeostasis.