DIABETES, OSTEOCALCIN, AND N-GLYCOAMINO ACIDS

我们发现从牛骨中分离的骨钙素 非酶糖基化。 这种糖基化的程度似乎 随着动物的年龄而变化，可能表明平均营业额 骨沉积的时间 由于非酶糖基化也是一种 个体的平均血糖状态的函数，问题 是否会出现一些与骨骼疾病有关的问题， 糖尿病可能反映了骨基质的异常过度糖基化 蛋白质如骨钙素。 我们打算检查一下 链脲佐菌素诱导的糖尿病大鼠骨钙素沉积。 我们还打算发展一种人体循环糖骨钙素的放射免疫测定法 基于对糖骨钙素的单克隆抗体。 测量 骨钙素将使用多克隆抗体进行， 骨钙素，我们已经制备和放射免疫法在我们的实验室。 糖骨钙素/骨钙素比值可能反映了成熟骨钙素的转换。 骨头 我们的工作假设是，新合成的骨钙素 没有糖基化，而骨沉积的骨钙素， 是. 因此，血清糖骨钙素的测量可能是一个 在测量骨疾病和骨损伤方面有价值的临床参数。 糖尿病 由于长寿命蛋白质如血红蛋白的氨基末端， 骨钙素、血清白蛋白、LDL-载脂蛋白和晶体蛋白成为 部分转化为N-（1-脱氧果糖-1-基）-氨基末端残基， 非酶糖基化，我们打算测量 尿中的N-（1-脱氧果糖基）-氨基酸。 这种测量可以产生 关于各种疾病中长寿命蛋白质周转的信息 包括糖尿病在内的疾病。 我们认为 在临床状态下，N-糖基酪氨酸/N-糖基缬氨酸比值应增加 其特征是骨丢失增加，部分反映了骨代谢的转换， 通过糖基血红蛋白的转换使糖基骨钙素正常化。

We have found that osteocalcin as isolated from bovine bone is nonenzymatically glycosylated. The extent of this glycosylation appears to vary with the age of the animal, perhaps indicating the average turnover time of the deposited bone. Since nonenzymatic glycosylation is also a function of the average glycemic status of the individual, the question arises as to whether or not some of the bone disease associated with diabetes mellitus might reflect abnormal over-glycosylation of bone matrix proteins such as osteocalcin. We intend to examine the levels of bone deposited glycoosteocalcin in the streptozotocin induced diabetic rat. We also intend to develop a RIA for circulating glycoosteocalcin in humans based on monoclonal antibodies raised to glycoosteocalcin. Measurements of osteocalcin will be carried out using the polyclonal antibody to osteocalcin which we have prepared and the RIA employed in our laboratory. The Glycoosteocalcin/Osteocalcin ratio may reflect the turnover of mature bone. Our working hypothesis assumes that newly synthesized osteocalcin is not glycosylated, whereas bone-deposited osteocalcin which turns over will be. Thus, measurement of serum glycoosteocalcin may turn out to be a valuable clinical parameter in the measurement of bone disease and in diabetes. Since amino terminals of long-lifed proteins such as hemoglobin, osteocalcin, serum albumin, LDL-apoprotein and the crystallins become converted in part to N-(1-deoxyfructos-1-yl)-amino terminal residues by nonenzymatic glycosylation, we intend to measure the content of N-(1-deoxyfructos-yl)-amino acids in urine. This measurement could yield information about the turnover of long-lifed proteins in various disease states including diabetes mellitus. We believe that the N-glycotyrosine/N-glycovaline ratio should increase in clinical states characterized by increased bone loss, reflecting, in part, the turnover of glycoosteocalcin normalized by the turnover of glycohemoglobin.