苹果酸酶存在于小鼠胰岛中，并调节胰岛素分泌。
Malic enzyme is present in mouse islets and modulates insulin secretion.
作者信息
Xu J, Han J, Long Y S, Lock J, Weir G C, Epstein P N, Liu Y Q
机构信息
Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville School of Medicine, Louisville, KY, USA.
出版信息
Diabetologia. 2008 Dec;51(12):2281-9. doi: 10.1007/s00125-008-1155-0. Epub 2008 Sep 19.
AIMS/HYPOTHESIS: The pyruvate-malate shuttle is a metabolic cycle in pancreatic beta cells and is important for beta cell function. Cytosolic malic enzyme (ME) carries out an essential step in the shuttle by converting malate to pyruvate and generating NADPH. In rat islets the pyruvate-malate shuttle may regulate insulin secretion and it has been shown to play a critical role in adaptation to obesity and insulin resistance. However, ME has not been demonstrated in mouse islets and three reports indicate that mouse islets contain no ME activity. If mouse islets lack ME, rat and mouse islets must regulate insulin secretion by different mechanisms.
METHODS
We measured ME activity by a fluorometric enzymatic assay and Me mRNA by real-time PCR. ME activity was also measured in streptozotocin-treated mouse islets. FACS-purified beta cells were obtained from MIP-GFP mouse islets, agouti-L obese mouse islets and mouse beta cell line MIN-6. Insulin secretion and NADPH/NADP(+) ratios were measured in Me siRNA-treated beta cells.
RESULTS
ME activity and Me mRNA were present in C57BL/6 mouse islets. ME activity was reduced in streptozotocin-treated mouse islets. ME activity was also measurable in FACS-purified mouse beta cells. In addition, ME activity was significantly increased in obese agouti-L mouse islets and the mouse MIN-6 cell line. Me siRNA inhibited ME activity and reduced glucose-stimulated insulin secretion and also inhibited NADPH products.
CONCLUSIONS/INTERPRETATION: Mouse islets contain ME, which plays a significant role in regulating insulin secretion.
目的/假设：丙酮酸 - 苹果酸穿梭是胰腺β细胞中的一种代谢循环，对β细胞功能很重要。胞质苹果酸酶（ME）通过将苹果酸转化为丙酮酸并生成NADPH，在该穿梭过程中执行关键步骤。在大鼠胰岛中，丙酮酸 - 苹果酸穿梭可能调节胰岛素分泌，并且已证明其在适应肥胖和胰岛素抵抗中起关键作用。然而，尚未在小鼠胰岛中证实存在ME，且有三篇报道表明小鼠胰岛不存在ME活性。如果小鼠胰岛缺乏ME，大鼠和小鼠胰岛必定通过不同机制调节胰岛素分泌。
方法
我们通过荧光酶法测定ME活性，并通过实时PCR测定Me mRNA。还在链脲佐菌素处理的小鼠胰岛中测量了ME活性。从MIP - GFP小鼠胰岛、刺豚鼠 - L肥胖小鼠胰岛和小鼠β细胞系MIN - 6中获得经荧光激活细胞分选（FACS）纯化的β细胞。在经Me siRNA处理的β细胞中测量胰岛素分泌和NADPH/NADP(+)比率。
结果
C57BL/6小鼠胰岛中存在ME活性和Me mRNA。链脲佐菌素处理的小鼠胰岛中ME活性降低。在经FACS纯化的小鼠β细胞中也可检测到ME活性。此外，肥胖的刺豚鼠 - L小鼠胰岛和小鼠MIN - 6细胞系中的ME活性显著增加。Me siRNA抑制ME活性，减少葡萄糖刺激的胰岛素分泌，并且还抑制NADPH产物。
结论/解读：小鼠胰岛含有ME，其在调节胰岛素分泌中起重要作用。
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