MECHANISM OF ISLET GROWTH AND DIFFERENTIATION

糖尿病，无论是胰岛素依赖型糖尿病还是非胰岛素依赖型糖尿病， 功能性胰腺β细胞的质量不足，在前者由于 对这些细胞的选择性自身免疫性破坏， 无法弥补肥胖或胰岛素的额外需求 阻力因此，一旦免疫破坏可以被阻止，两种类型的 糖尿病是可以治疗的，如果我们知道如何刺激 体内或体外的β细胞。在研究的所有组织中， 增长需要大量刺激和增长的复杂协调 因素部分胰腺切除术大鼠模型是一种定义明确的模型， β细胞和胰腺细胞的生长， 研究胰腺中这一过程的调节。在这个模型中， 胰腺的再生通过两种途径发生：复制前 存在的胰腺β细胞和导管上皮细胞的扩张 并随后分化成内分泌和外分泌组织。 来自该模型和来自过度表达TGF-β 1的转基因小鼠的数据 α：提供了成人中前体细胞的第一个有力证据 胰管体内和体外实验都被提议用于 表征这些假定的前体细胞，并探索是否有 外分泌细胞和内分泌细胞是分开的。在此 再生几种生长因子（TGF-β，IGF-I，肝细胞生长 因子）显示其表达的显著变化，如通过RNA检测的 分析和免疫化学;这些变化表明参与 这些因素在这个过程中。这些因素的作用 因为TGF-α和胃泌素将在培养的导管上皮上进行测试， 在培养的胰岛单层上测定其对增殖的作用， 这些细胞的形态发生和分化。此外 上皮-间充质相互作用和3 这些效应中的每一个的导管细胞的维度组织 将被评估。根据这些实验场景的数据， 因子的相互作用可以使用类似的方案在 努力在体外重建定义和结构化的序列， 发生在体内的事件。这些实验应该提供一个更好的 了解胰腺生长和分化的调节。 了解如何刺激胰岛细胞的生长和分化 可能会带来新的疗法。

Diabetes mellitus, whether IDDM or NIDDM, can be considered the result of inadequate mass of functional pancreatic beta cells, in the former due to a selective autoimmune destruction of these cells and in the latter to an inability to compensate for the extra demand of obesity or insulin resistance. Thus once immune destruction can be arrested,both types of diabetes could be treated if we knew how to stimulate the expansion of the beta-cells in vivo or in vitro. In all tissues studied the regulation of growth requires a complex orchestration of numerous stimuli and growth factors. The partial pancreatectomy rat model is a well defined model of beta- cell and pancreatic cell growth-that offers the opportunity to study the regulation of this process in the pancreas. In this model-the regeneration of pancreas occurs by two pathways: replication of pre- existing pancreatic beta-cells and by expansion of the duct epithelium and its subsequent differentiation into endocrine and exocrine tissue. Data from this model and from transgenic mice that over-express TGF- alpha: provide the first strong evidence of precursor cells in the adult pancreatic ducts. Both in vivo and in vitro experiments are proposed to characterize these putative precursor cells and to explore whether there are separate populations for exocrine and endocrine cells. During this regeneration several growth factors (TGF-beta, IGF-I, hepatocyte growth factor) show significant changes in their expression as measured by RNA analysis and immunochemistry; these changes suggest the involvement of these factors in the process. The role of each of these factors as well as TGF-alpha and gastrin will be tested on cultured duct epithelium and on cultured islet monolayers to determine its effect on proliferation, morphogenesis and differentiation of these cells. In addition the requirements for epithelial-mesenchymal interactions and for 3 dimensional organization of the ductal cells for each of these effects will be assessed. With the data from these experiments scenarios for interactions of factors can be tested using similar protocols in an effort to reconstruct in vitro the defined and structured sequence of events that occur in vivo. These experiments should provide a better understanding of the regulation of pancreatic growth and differentiation. Knowledge of how to stimulate growth and differentiation of islet cells may lead to new therapies.