MECHANISMS OF ADULT HUMAN ISLET PROLIFERATION

成人胰岛在使用纯化的层粘连蛋白-5细胞外基质培养时增殖。这种体外增殖成人胰岛的能力在通过移植治疗糖尿病方面具有直接的潜在应用，但更重要的是，这使得研究成人胰岛增殖的机制变得容易。了解胰岛在培养中扩张时发生的过程可能会导致新的治疗方法，以恢复糖尿病患者足够的β细胞质量。这项研究的总体目标是了解导致成人胰岛体外增殖的机制。具体目标如下：1)充分确定成人胰岛在培养过程中发生的形态和功能表型变化的顺序。2)确定控制表型变化和调控体外成人胰岛增殖的因素。最近，一些控制胰岛激素产生的基因转录因子也被发现在胰腺的发育中起着关键作用。拟议的实验特别关注这些转录因子，因为它们很可能在培养的成人胰岛增殖过程中受到调控。为了实现这些目标，成人胰岛将在体外增殖，并使用细胞和分子方法进行检测。

Adult human islets proliferate when cultured using purified laminin-5 extracellular matrix. This ability to proliferate adult human islets ex-vivo has direct potential application to the treatment of diabetes through transplantation, but more importantly, readily allows the mechanisms of adult human islet proliferation to be studied. Understanding the processes occurring when islets expand in culture may lead to novel treatments to restore an adequate beta cell mass in diabetic patients. The overall objective of this research proposal is to understand the mechanisms leading to the ex vivo proliferation of adult human islets. The specific aims are as follows: 1) Determine fully the sequence of morphological and functional phenotype changes that occur when adult human islets proliferate in culture. 2) Determine the factors controlling the phenotype changes and regulating ex vivo adult human islet proliferation. Recently several gene transcription factors that control islet hormone production have in addition been found to play critical roles in the development of the pancreas. The proposed experiments are particularly focused on these transcription factors because they are very likely to be regulated during adult human islet proliferation in culture. To accomplish these objectives adult human islets will be proliferated ex vivo, and examined using cellular and molecular methods.