Effect of ghrelin on pancreas beta cells and diabetic animal models

生长素释放肽对胰腺β细胞和糖尿病动物模型的影响

基本信息

批准号：
17390269
负责人：
AKAMIZU Takashi
金额：
$ 9.79万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390269/
关键词：
Ghrelin Diabetes Pancreatic beta cell Insulin 膵臓β細胞

项目摘要

Ghrelin, a stomach-derived hormone, functions in multiple biological processes, including glucose metabolism and cellular differentiation and proliferation. In this study, we examined 'if early treatment with ghrelin can regenerate β cells of the pancreas in an animal model of diabetes mellitus, the nO-STZ model in which neonatal rats are injected with streptozotocin (STZ) at birth. Following administration of ghrelin to nO-STZ rats from postnatal days 2 to 8, we examined β-cell mass, mRNA expression levels of insulin and pdx-1 (pancreatic duodenal homeobox 1), and pancreatic morphology on days 21 and 70. In addition, we investigated the effects of ghrelin on β-cell replication. By day 21, ghrelin treatment increased pancreatic expression of insulin and pdx-1 mRNA in nO-STZ rats. The number of replicating cells was also significantly increased in the ghrelin-treated nO-STZ model. At day 70, nO-STZ rats exhibited hyperglycemia, despite slight increases in plasma insulin levels. Ghrelin treatment resulted in the improvement of plasma glucose levels associated with normal plasma insulin levels. Pancreatic insulin mRNA and protein levels were significantly increased in ghrelin-treated nO-STZ model animals. These findings suggest that ghrelin promotes regeneration of β cells in STZ-treated newborn rats. Furthermore, we attempted to examine effects of ghrelin on other diabetes models including adult STZ-injected rats, SDT (Spontaneously Diabetic Torii) rat and NOD (Non-obese diabetic) mice. In addition, we investigated effects of desacyl ghrelin on nO-STZ rats and found that desacyl ghrelin tended to prevent the development of hyperglycemia in this model.

Ghrelin是摊位衍生的马龙，在多种生物学过程中起作用，包括葡萄糖代谢，细胞分化和增殖。在这项研究中，我们检查了“如果早期用生长素蛋白可以在糖尿病的动物模型中再生胰腺的β细胞，那是新生大鼠出生时向新生大鼠注射新生大鼠的NO-STZ模型。从产后第2天到第8天将生长素释放到NO-STZ大鼠之后，我们检查了β细胞质量，胰岛素和PDX-1的mRNA表达水平（胰十二指肠同源蛋白蛋白蛋白蛋白蛋白酶1）以及第21和70天的胰腺形态。此外，我们还研究了ghrelin对β-纤维蛋白重复的影响。到第21天，生长素治疗增加了NO-STZ大鼠中胰岛素和PDX-1 mRNA的胰腺表达。在经过血清素处理的NO-STZ模型中，复制细胞的数量也显着增加。在第70天，NO-STZ大鼠暴露了高血糖，等离子体胰岛素水平的层略有增加。生长素素治疗导致与正常血浆胰岛素水平相关的血浆葡萄糖水平提高。胰岛素治疗的NO-STZ模型动物中胰腺胰岛素mRNA和蛋白质水平显着增加。这些发现表明，生长素蛋白促进了经STZ处理的新生大鼠中β细胞的再生。此外，我们试图检查生长素素对其他糖尿病模型的影响，包括成人STZ注射大鼠，SDT（自发性糖尿病Torii）大鼠和点头（非肥胖糖尿病）小鼠。此外，我们调查了避难所的杀伤力对NO-STZ大鼠的作用，发现避孕药llelin倾向于防止该模型中高血糖的发展。