DIABETES, OSTEOCALCIN, AND N-GLYCOAMINO ACIDS

点击翻译按钮获取中文摘要

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.