Taylor-Fishwick David A, Bowman Angela, Hamblet Natasha, Bernard Paul, Harlan David M, Vinik Aaron I
Department of Internal Medicine, Eastern Virginia Medical School, 855 W Brambleton Avenue, Norfolk, 23510 Virginia, USA.
J Endocrinol. 2006 Sep;190(3):729-37. doi: 10.1677/joe.1.06698.
Islet neogenesis associated protein (INGAP) is a protein factor that can stimulate new islet mass from adult pancreatic progenitor cells. In models of islet neogenesis, INGAP expression is elevated in pancreatic acinar cells. Using a transgenic model to drive a sustained expression of INGAP in pancreatic acinar cells, we have identified a protection to chemical-induced hyperglycemia. A sustained expression of INGAP during development did not perturb islet development or basal blood glucose homeostasis, although beta-cell mass and pancreatic insulin content were significantly increased in the INGAP transgenic mice. When challenged with a diabetogenic dose of streptozotocin (STZ), mice carrying the INGAP transgene did not become hyperglycemic. In contrast, wild-type mice became and remained hyperglycemic, blood glucose > 550 mg/dl. The serum insulin levels and islet morphology were preserved in the transgenic mice after STZ treatment. These data suggest that the sustained expression of INGAP in the acinar pancreas confers resistance to a diabetogenic insult. The INGAP transgenic mouse provides a new model to uncover factors that are protective to diabetes onset and biomarkers to track beta-cell pathology.
胰岛新生相关蛋白（INGAP）是一种能够刺激成年胰腺祖细胞产生新胰岛团块的蛋白质因子。在胰岛新生模型中，INGAP在胰腺腺泡细胞中的表达升高。利用转基因模型驱动INGAP在胰腺腺泡细胞中持续表达，我们发现其对化学诱导的高血糖具有保护作用。尽管INGAP转基因小鼠的β细胞数量和胰腺胰岛素含量显著增加，但在发育过程中INGAP的持续表达并未干扰胰岛发育或基础血糖稳态。当用致糖尿病剂量的链脲佐菌素（STZ）进行攻击时，携带INGAP转基因的小鼠并未出现高血糖。相比之下，野生型小鼠出现并持续处于高血糖状态，血糖>550mg/dl。STZ处理后，转基因小鼠的血清胰岛素水平和胰岛形态得以保留。这些数据表明，INGAP在腺泡胰腺中的持续表达赋予了对致糖尿病损伤的抗性。INGAP转基因小鼠为揭示对糖尿病发病具有保护作用的因素以及追踪β细胞病理变化的生物标志物提供了一个新模型。
