DIABETES, OSTEOCALCIN, AND N-GLYCOAMINO ACIDS

我们发现从牛骨中分离出的骨钙素是 非酶糖基化的。这种糖基化的程度似乎是 随着动物年龄的不同而变化，也许表明了平均周转率 骨沉积的时间。因为非酶糖基化也是一种 个人平均血糖水平的作用，这个问题 是否一些与骨病有关的骨病 糖尿病可能反映骨基质异常过度糖基化 蛋白质，如骨钙素。我们打算检查骨骼的水平 链脲佐菌素诱导的糖尿病大鼠体内糖化骨钙素的沉积。 我们还打算建立一种用于人类体内糖化骨钙素循环的放射免疫分析方法。 基于对糖化骨钙素产生的单抗。测量 骨钙素将使用多克隆抗体进行 我们制备的骨钙素和我们实验室使用的放射免疫法。 糖化骨钙素/骨钙素比值可反映成熟卵巢的周转。 骨头。我们的工作假设是，新合成的骨钙素是 不是糖基化的，而骨沉积的骨钙素会 是.。因此，血清糖化骨钙素的测定可能成为一种 在骨病测量中有价值的临床参数 糖尿病。 由于长寿命蛋白质的氨基末端，如血红蛋白， 骨钙素、血清白蛋白、低密度脂蛋白和晶状体蛋白 部分转化为N-(1-脱氧果糖-1-基)氨基末端残基 非酶糖基化，我们打算测定的含量 尿中N-(1-脱氧果糖)-氨基酸。这一措施可能会产生 长寿命蛋白质在各种疾病中周转的信息 包括糖尿病在内的国家。我们相信， 临床状态下N-糖基酪氨酸/N-氨基葡萄糖苷比值应升高 以骨丢失增加为特征的，部分反映了 糖化糖钙素通过糖化血红蛋白的周转而归一化。

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.