INSULIN AND HGH: SECRETION AND 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）研究特异性结合蛋白的作用， 控制IGF的作用，（3）确定这些因素在 正常的生长和发育，特别是与青春期有关的 生长和性成熟。 在上述第一类中，我们将研究 胰岛素样生长因子（IGF I和IGF II）的作用， 生长激素（GH）对新生血管形成的两个关键步骤的作用 视网膜：首先，这些因素在控制视网膜的作用， 毛细血管基底膜和周围基质的溶解 视网膜内皮细胞和第二，这些药物的作用， 控制视网膜内皮细胞随后的迁移 （趋化性）。 用于测量胶原酶III和IV的酶测定 和技术的研究趋化性是功能的原则 调查员实验室 在初步工作中，我们已经证明， IGF I和GH均影响上述每个主要步骤。 的能力 周细胞、视网膜色素上皮细胞和其他物质 玻璃体调节IGF和GH的行动将全面检查， 体外和体内研究。 人视网膜内皮细胞，色素 为此目的，将上皮细胞和周细胞维持在培养物中 我们根据需要获取牛细胞。 我们将同样继续对结合的血清蛋白进行表征， IGF I和II，特别强调这些蛋白质在 主要病理状态。 这些结合蛋白的重要性在于， 它们无疑改变了增长的分布和作用， 因素 我们将研究IGF I和II在调节正常的 特别强调界定互联网治理论坛的作用 I在控制正常青春期生长和控制载体蛋白方面 表情 我们有能力检测特异性IGF I和IGF II， 以及IGF研究参与的多个过程的能力， 新生血管形成 我们在生物化学方面取得了重大进展， IGF载体蛋白的纯化。 到高级调查员的 在美国没有一个实验室 具有相当的能力，并有记录证明这种能力。

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.