METABOLIC FUELS, DIABETES AND SOMATOMEDIN ACTIVITY

虽然糖尿病和营养不良的不良增长归因于减少 营养素的利用，缺陷的机制尚不清楚。 骨骼 生长归因于生长调节素对软骨的刺激， 具有广泛的合成代谢作用的因素。 其他循环因子，抑制剂，可能 限制生长调节素的作用;净生长调节素的生物测定 活性反映生长调节素和抑制剂。 我们的研究表明， 生长调节素和抑制剂可以通过色谱法分离， 这两种因素都是由肝脏根据胰岛素产生的， 营养状况 虽然生长调节素和抑制剂的改变可能 直接利用营养物质或远离生长，控制过程 我们对此知之甚少。 为了阐明潜在的机制， 提出了努力。 1)为了评估体内胰岛素和营养的调节， 将在人类中检查循环生长调节素和抑制剂，a） 不同的糖尿病控制，B）营养不良和恢复，以及c） 饮食诱导的体重减轻，和d）具有广泛代谢的大鼠 改变。 2)为了研究肝脏作为假定的调节位点， 生长调节素和抑制剂的“形成”将通过联合肝脏测量。 提取和灌注，并与肝脏燃料代谢的探针相关， 肝脏响应a）外部稳态需求（施加的改变， 胰岛素和营养）和B）内部需求（部分 肝切除术）。 3)研究养分利用的潜在调节 根据生成的生长调节素和抑制剂的平衡， 将在体外和体内对软骨、肌肉和脂肪组织进行检查。 4)这些生理实验将伴随着物理化学的努力 a）增强生长调节素和抑制剂从 生物样品，和B）进一步改进用于生物样品的制剂， 特征化 这些研究应有助于更好地了解 调节正常生长，了解受损的病理生理学 生长，以及治疗糖尿病生长障碍的新概念， 营养不良

Although poor growth in diabetes and malnutrition is attributed to decreased utilization of nutrients, the mechanism of the defect is not known. Skeletal growth is attributed to stimulation of cartilage by somatomedins, circulating factors with broad anabolic effects. Other circulating factors, inhibitors, may limit the actions of somatomedins; bioassay measurements of net somatomedin activity reflect both somatomedins and inhibitors. Our studies suggest that somatomedins and inhibitors can be separated by chromatographic procedures, and that both factors are generated by the liver according to insulin and nutritional status. While alterations in somatomedins and inhibitors might direct utilization of nutrients toward or away from growth, control processes are poorly understood. To elucidate underlying mechanisms, the following efforts are proposed. 1) To assess regulation by insulin and nutrition in vivo, circulating somatomedins and inhibitors will be examined in humans with a) varying diabetic control, b) malnutrition and realimentation, and c) diet-induced weight loss, and d) rats with a wide range of metabolic alterations. 2) To study the liver as the putative locus of regulation, net "formation" of somatomedins and inhibitors will be measured via combined liver extraction and perfusion, and related to probes of hepatic fuel metabolism as the liver responds to a) external homeostatic demands (imposed alterations in insulin and nutrition) and b) internal demands (restoration after partial hepatectomy). 3) To investigate potential modulation of nutrient utilization according to the balance of generated somatomedins and inhibitors, interactions will be examined on cartilage, muscle, and adipose tissue in vitro and in vivo. 4) These physiologic experiments will be accompanied by physicochemical efforts to a) enhance separation and recovery of somatomedins and inhibitors from biological samples, and b) further improve preparations for biological characterization. These studies should provide improved understanding of the regulation of normal growth, insight into the pathophysiology of impaired growth, and new concepts for therapy of growth failure in diabetes mellitus and malnutrition.