Pihlajaniemi T, Myllylä R, Kivirikko K I, Tryggvason K
J Biol Chem. 1982 Dec 25;257(24):14914-20.
The influence of streptozotocin diabetes, glucose, and insulin on the metabolism of basement membrane collagen and proteoglycan was studied in the murine EHS tumor. No differences were found in the amino acid composition of tumors grown in diabetic and control mice, suggesting that the relative amount of collagen was not increased. Similarly, no significant differences were observed in any of the intracellular enzyme activities of collagen biosynthesis in the tumor tissue, but in diabetic mice, a significant increase was found in all four enzyme activities studied in the kidneys. High glucose concentrations increased total protein synthesis of the tumor tissue in vitro whereas insulin had no effect. Basement membrane collagen synthesis was also increased but to the same extent as protein synthesis in general. No qualitative changes were found in the pro-alpha 1(IV) and pro-alpha 2(IV) chains synthesized in vitro with or without insulin at different glucose concentrations. Hyperglycemia secondary to insulin deficiency may thus be responsible for the basement membrane thickening in diabetes but this cannot explain the relative increase in collagen content of these matrices. The incorporation of 35SO4 into proteoglycan in vitro was likewise increased at high glucose concentrations, indicating that the synthesis of this component may also be altered in diabetes.
研究了链脲佐菌素诱导的糖尿病、葡萄糖和胰岛素对小鼠EHS肿瘤基底膜胶原蛋白和蛋白聚糖代谢的影响。在糖尿病小鼠和对照小鼠体内生长的肿瘤的氨基酸组成没有差异，这表明胶原蛋白的相对含量没有增加。同样，肿瘤组织中胶原蛋白生物合成的任何细胞内酶活性均未观察到显著差异，但在糖尿病小鼠中，所研究的肾脏中所有四种酶活性均显著增加。高葡萄糖浓度增加了肿瘤组织在体外的总蛋白质合成，而胰岛素则没有影响。基底膜胶原蛋白合成也增加了，但与一般蛋白质合成的程度相同。在不同葡萄糖浓度下，无论有无胰岛素，体外合成的前α1(IV)和前α2(IV)链均未发现定性变化。胰岛素缺乏继发的高血糖可能是糖尿病中基底膜增厚的原因，但这无法解释这些基质中胶原蛋白含量的相对增加。在高葡萄糖浓度下，体外将35SO4掺入蛋白聚糖的过程同样增加，这表明该成分的合成在糖尿病中也可能发生改变。
