Ghrelin prevents development of diabetes at adult age in streptozotocin-treated newborn rats
Ghrelin prevents development of diabetes at adult age in streptozotocin-treated newborn rats
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DOI：
10.1007/s00125-006-0226-3
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发表时间：
2006-06-01
期刊：
影响因子：
8.2
通讯作者：
Kangawa, K
中科院分区：
文献类型：
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作者：
Irako, T;Akamizu, T;Kangawa, K
目的/假设：Ghrelin是一种胃源性激素，在多种生物学过程中发挥作用，包括葡萄糖代谢和细胞分化与增殖。在这项研究中，我们研究了早期治疗与生长激素释放肽是否可以再生β细胞的胰腺在糖尿病的动物模型，n 0-STZ模型，其中新生大鼠在出生时注射链脲佐菌素（STZ）。研究方法：出生后第2天至第8天给予生长激素释放肽给n 0-STZ大鼠，我们在第21天和第70天检查了β细胞质量、胰岛素和胰腺和十二指肠同源框1（Pdx 1）基因的mRNA表达水平以及胰腺形态。此外，我们还研究了ghrelin对β细胞复制的影响。结果：到第21天，ghrelin治疗增加了n 0-STZ大鼠胰腺胰岛素和Pdx 1 mRNA的表达。在ghrelin处理的n 0-STZ模型中，复制细胞的数量也显著增加。在第70天，n 0-STZ大鼠表现出高血糖症，尽管血浆胰岛素水平略有增加。Ghrelin治疗导致血浆葡萄糖水平的改善，这与正常的血浆胰岛素水平相关。在ghrelin处理的n 0-STZ模型动物中，胰腺胰岛素mRNA和蛋白水平显著增加。结论/解释：这些发现表明，生长激素释放肽促进再生的β细胞在STZ治疗的新生大鼠。因此，早期给予生长激素释放肽可能有助于预防易患病受试者在β细胞破坏后发生糖尿病。
Aims/hypothesis: Ghrelin, a stomach-derived hormone, functions in multiple biological processes, including glucose metabolism and cellular differentiation and proliferation. In this study, we examined whether early treatment with ghrelin can regenerate beta cells of the pancreas in an animal model of diabetes mellitus, the n0-STZ model, in which neonatal rats are injected with streptozotocin (STZ) at birth. Methods: Following administration of ghrelin to n0-STZ rats from postnatal days 2 to 8, we examined beta cell mass, mRNA expression levels of insulin and of pancreatic and duodenal homeobox 1 (Pdx1) gene, and pancreatic morphology on days 21 and 70. In addition, we investigated the effects of ghrelin on beta cell replication. Results: By day 21, ghrelin treatment increased pancreatic expression of insulin and Pdx1 mRNA in n0-STZ rats. The number of replicating cells was also significantly increased in the ghrelin-treated n0-STZ model. At day 70, n0-STZ rats exhibited hyperglycaemia, despite slight increases in plasma insulin levels. Ghrelin treatment resulted in the improvement of plasma glucose levels, which were associated with normal plasma insulin levels. Pancreatic insulin mRNA and protein levels were significantly increased in ghrelin-treated n0-STZ model animals. Conclusions/interpretation: These findings suggest that ghrelin promotes regeneration of beta cells in STZ-treated newborn rats. Thus, early administration of ghrelin may help prevent the development of diabetes in disease-prone subjects after beta cell destruction.