INSULIN & HIGH: SECRETION & METABOLIC ACTIONS

我们的调查工作将集中在三个方面：(1)确定 胰岛素样生长因子在糖尿病发病中的作用 视网膜病变，(2)研究特定结合蛋白在视网膜病变中的作用 控制IGF的作用，以及(3)定义这些因素在 正常的生长和发育，尤其是与青春期有关的 生长和性成熟。在上面的第一类中，我们将研究 胰岛素样生长因子(IGF-I和IGF-II)和 生长激素(GH)参与血管新生的两个关键步骤 视网膜：首先，这些因素在控制视网膜功能中的作用 毛细血管基底膜及其周围基质的溶解 第二，这些药物在视网膜内皮细胞中的作用 控制视网膜内皮细胞的后续迁移 (趋化性)。酶法测定胶原酶III和IV 而研究趋化性的技术在原理上是有用的 调查员的实验室。在前期工作中，我们已经证明了 胰岛素样生长因子I和生长激素都会影响上面列出的每个主要步骤。一种能力 周细胞、视网膜色素上皮细胞和其他物质 玻璃体调节胰岛素样生长因子和生长激素的作用将在 体外和体内研究。人视网膜内皮细胞，色素 为此目的，在培养中维持上皮细胞和周细胞 我们会根据需要获取牛细胞。 我们还将继续对结合的血清蛋白进行鉴定 IGF I和II，特别强调这些蛋白质在 主要的病理状态。这些结合蛋白是非常重要的 它们毫无疑问地改变了增长的分布和作用。 各种因素。我们将研究IGF I和II在调节正常中的作用 增长和发展，特别强调界定政府间发展论坛的作用 I在控制正常青春期生长和控制载体蛋白中的作用 表情。我们有能力专门检测IGF I和IGF II作为 以及IGF研究涉及到的多个过程的能力 新生血管。我们在生物化学方面取得了重大进展 胰岛素样生长因子载体蛋白的纯化。致高级调查员的 知识在美国没有一家实验室拥有 可比能力和证明这一能力的记录。

Our investigative efforts will be concentrated in 3 areas: (1) determining the role of the insulin-like growth factors in the development of diabetic retinopathy, (2) investigating the role of specific binding proteins in controlling IGF action, and (3) defining the role of these factors in normal growth and development, particularly as they relate to pubertal growth and sexual maturation. In the first category above, we will study the actions of the insulin-like growth factors (IGF I and IGF II) and growth hormone (GH) on two critical steps involved in neovascularization of the retina: First, the role of these factors in controlling the dissolution of capillary basement membranes and the matrix which surrounds retinal endothelial cells and second, the action of these agents in controlling subsequent migration of retinal endothelial cells (chemotaxis). Enzyme assays for the measurement of collagenase III and IV and techniques for the study of chemotaxis are functional in the Principle Investigator's laboratory. In preliminary work we have demonstrated that both IGF I and GH effect each of the major steps listed above. The ability of pericytes, retinal pigment epithelial cells and other substances in vitreous to modulate IGF and GH action will be examined comprehensively in in vitro and in vivo studies. Human retinal endothelial cells, pigment epithelial cells, and pericytes are maintained in culture for this purpose and we obtain bovine cells as needed. We will likewise continue characterization of the serum proteins that bind IGF I and II with particular emphasis on the role of these proteins in major pathological states. These binding proteins are important in that they unquestionably alter both the distribution and action of the growth factors. We will investigate the role of IGF I and II in modulating normal growth and development with particular emphasis on defining the role of IGF I in controlling normal pubertal growth and in controlling carrier protein expression. We have the capacity to assay specifically IGF I and IGF II as well as the capacity for IGF to study multiple processes involved in neovascularization. We have made major advances in the biochemical purification of the carrier proteins for IGF. To the Senior Investigator's knowledge there is no single laboratory in the United States with comparable capacity and a record that demonstrates this capacity.