Transgenic overexpression of intraislet ghrelin does not affect insulin secretion or glucose metabolism in vivo
Transgenic overexpression of intraislet ghrelin does not affect insulin secretion or glucose metabolism in vivo
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DOI：
10.1152/ajpendo.00341.2011
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发表时间：
2012-02-01
影响因子：
5.1
通讯作者：
Akamizu, Takashi
中科院分区：
文献类型：
--
作者：
Bando, Mika;Iwakura, Hiroshi;Akamizu, Takashi
Bando M，Iwakura H，Ariyasu H，Hosoda H，Yamada G，Hosoda K，阿达奇S，Nakao K，Kangawa K，Akamizu T.胰岛内ghrelin的转基因过表达不影响体内胰岛素分泌或葡萄糖代谢。Am J Physiol Endocrinol Metab 302：E403-E408，2012.首次发表于2011年11月22日; doi：10.1152/ajpendo.00341.2011.-而ghrelin主要在胃中产生，少量的它在胰岛中产生。虽然外源性给予ghrelin在体外或体内抑制胰岛素分泌，但胰岛内ghrelin在体内调节胰岛素分泌中的作用仍不清楚。为了了解胰岛内ghrelin在胰岛素分泌和葡萄糖代谢中的生理作用，我们开发了一种转基因（Tg）小鼠模型，大鼠胰岛素II启动子ghrelin-内部核糖体进入位点-ghrelin O-酰基转移酶（RIP-GG）Tg小鼠，其中小鼠ghrelin cDNA和ghrelin O-酰基转移酶在大鼠胰岛素II启动子的控制下过表达。尽管RIP-GG Tg小鼠的胰腺去酰基生长素水平升高，但在标准饮食的动物中，胰腺生长素水平没有改变。然而，当给Tg小鼠喂食富含中链甜菜碱的饮食（MCTD）时，胰腺ghrelin水平升高至对照动物的16倍。胃饥饿素细胞似乎具有提供饥饿素酰化所必需的辛酰酸的特定机制，但胰腺β细胞中不存在这种机制。尽管生长素释放肽过表达，但RIP-GG Tg小鼠门静脉中的血浆生长素释放肽水平与对照水平相比没有变化。RIP-GG Tg小鼠的葡萄糖耐量、胰岛素分泌和胰岛结构即使在喂食MCTD时也没有显著差异。这些结果表明，胰岛内生长素释放肽在体内胰岛素分泌的调节中不起主要作用。
Bando M, Iwakura H, Ariyasu H, Hosoda H, Yamada G, Hosoda K, Adachi S, Nakao K, Kangawa K, Akamizu T. Transgenic overexpression of intraislet ghrelin does not affect insulin secretion or glucose metabolism in vivo. Am J Physiol Endocrinol Metab 302: E403-E408, 2012. First published November 22, 2011; doi: 10.1152/ajpendo.00341.2011.-Whereas ghrelin is produced primarily in the stomach, a small amount of it is produced in pancreatic islets. Although exogenous administration of ghrelin suppresses insulin secretion in vitro or in vivo, the role of intraislet ghrelin in the regulation of insulin secretion in vivo remains unclear. To understand the physiological role of intraislet ghrelin in insulin secretion and glucose metabolism, we developed a transgenic (Tg) mouse model, rat insulin II promoter ghrelin-internal ribosomal entry site-ghrelin O-acyl transferase (RIP-GG) Tg mice, in which mouse ghrelin cDNA and ghrelin O-acyltransferase are overexpressed under the control of the rat insulin II promoter. Although pancreatic desacyl ghrelin levels were elevated in RIP-GG Tg mice, pancreatic ghrelin levels were not altered in animals on a standard diet. However, when Tg mice were fed a medium-chain triglyceride-rich diet (MCTD), pancreatic ghrelin levels were elevated to similar to 16 times that seen in control animals. It seems likely that the gastric ghrelin cells possess specific machinery to provide the octanoyl acid necessary for ghrelin acylation but that this machinery is absent from pancreatic beta-cells. Despite the overexpression of ghrelin, plasma ghrelin levels in the portal veins of RIP-GG Tg mice were unchanged from control levels. Glucose tolerance, insulin secretion, and islet architecture in RIP-GG Tg mice were not significantly different even when the mice were fed a MCTD. These results indicate that intraislet ghrelin does not play a major role in the regulation of insulin secretion in vivo.