Rat neonatal beta cells lack the specialised metabolic phenotype of mature beta cells.
Rat neonatal beta cells lack the specialised metabolic phenotype of mature beta cells.
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DOI：
10.1007/s00125-010-2036-x
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发表时间：
2011-03
期刊：
影响因子：
8.2
通讯作者：
Bonner-Weir, S.
中科院分区：
文献类型：
--
作者：
Jermendy, A.;Toschi, E.;Aye, T.;Koh, A.;Aguayo-Mazzucato, C.;Sharma, A.;Weir, G. C.;Sgroi, D.;Bonner-Weir, S.
胎儿和新生儿的β细胞在葡萄糖诱导下的胰岛素分泌很差，只有在出生几周后才能获得强劲的葡萄糖反应。我们假设这种无反应是由于通常在β细胞中发现的代谢途径的普遍不成熟所致，而不是由于特定的缺陷。我们利用激光捕获显微解剖技术，从出生后第1天(P1)的新生和年轻成年Spraogue-Dawley大鼠的胰岛中切除了富含β细胞的核心，以比较它们的基因表达谱，并使用Affymetrix U34A微阵列(新生儿，4只；成年，3只)。经dChip软件分析，新生儿胰岛β细胞富集区的217个基因探针/38个表达序列标签(EST)显著高于成人胰岛，345个基因/33个EST显著低于成人胰岛。在新生儿β细胞中表达较低的基因包括线粒体穿梭(苹果酸脱氢酶、甘油-3-磷酸脱氢酶和谷草转氨酶)、丙酮酸羧基转移酶和肉碱棕榈酰转移酶2等关键代谢基因。通过对分离的新生儿(P2~P28)和成人胰岛RNA进行定量PCR和胰腺免疫染色，证实这些酶基因的差异表达。即使在28天大的时候，其中一些基因的表达水平仍然低于成人。新生儿胰岛缺乏葡萄糖反应很可能是由于胰岛β细胞代谢特化的普遍不成熟所致。
Fetal and neonatal beta cells have poor glucose-induced insulin secretion and only gain robust glucose responsiveness several weeks after birth. We hypothesise that this unresponsiveness is due to a generalised immaturity of the metabolic pathways normally found in beta cells rather than to a specific defect. Using laser-capture microdissection we excised beta cell-enriched cores of pancreatic islets from day 1 (P1) neonatal and young adult Sprague–Dawley rats in order to compare their gene-expression profiles using Affymetrix U34A microarrays (neonatal, n=4; adult, n=3). Using dChip software for analysis, 217 probe sets for genes/38 expressed sequence tags (ESTs) were significantly higher and 345 probe sets for genes/33 ESTs significantly lower in beta cell-enriched cores of neonatal islets compared with those of adult islets. Among the genes lower in the neonatal beta cells were key metabolic genes including mitochondrial shuttles (malate dehydrogenase, glycerol-3-phosphate dehydrogenase and glutamate oxalacetate transaminase), pyruvate carboxylase and carnitine palmitoyl transferase 2. Differential expression of these enzyme genes was confirmed by quantitative PCR on RNA from isolated neonatal (P2 until P28) and adult islets and with immunostaining of pancreas. Even by 28 days of age some of these genes were still expressed at lower levels than in adults. The lack of glucose responsiveness in neonatal islets is likely to be due to a generalised immaturity of the metabolic specialisation of pancreatic beta cells.
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影响因子：
4.8
作者：
Hasan, Noaman M.;Longacre, Melissa J.;MacDonald, Michael J.
通讯作者：
MacDonald, Michael J.
影响因子：
4.8
作者：
Guay, Claudiane;Madiraju, S. R. Murthy;Prentki, Marc
通讯作者：
Prentki, Marc
影响因子：
7.7
作者：
LAVINE, RL;CHICK, WL;MAKDISI, TW
通讯作者：
MAKDISI, TW
影响因子：
7.7
作者：
Brun, T;Roche, E;Prentki, M
通讯作者：
Prentki, M
影响因子：
7.7
作者：
HELLERSTROM, C;SWENNE, I
通讯作者：
SWENNE, I