Spanheimer R G, Umpierrez G E, Stumpf V
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30303.
Diabetes. 1988 Apr;37(4):371-6. doi: 10.2337/diab.37.4.371.
Many of the chronic complications of diabetes mellitus involve defects in the connective tissue such as poor wound healing, diminished bone formation, and decreased linear growth. Because collagen is the major protein component of these connective tissues, we examined collagen production in diabetic rats as a probe of this generalized defect in connective tissue metabolism. Doses of streptozocin ranging from 35 to 300 mg/kg were used to induce diabetes of graded metabolic severity in rats. Parietal bone or articular cartilage was removed and incubated at 37 degrees C with 5 microCi L-[5-3H]proline for 2 h, and collagen and noncollagen protein production were quantitated after separation with purified bacterial collagenase. Within 2 wk after induction of diabetes, collagen production was significantly reduced in bone and cartilage from diabetic rats to 52% (P less than .01) and 51% (P less than .01) of control (buffer-injected) levels, respectively. In contrast, noncollagen protein production in bone and cartilage from diabetic animals was no different from in tissue from control rats. The correlation between collagen relative to total protein production (relative rate) and the degree of hyperglycemia was highly significant for both bone (r = -.77, P less than .001) and cartilage (r = -.87, P less than .001). Other factors found to correlate with altered collagen production were the duration of diabetes and the amount of weight loss. Thus, diabetes is associated with a marked decrease in collagen production, which was seen early after induction of diabetes and was specific when compared with noncollagen protein production. Cumulative effects of these marked changes in collagen production may contribute to the chronic connective tissue complications in diabetes.
糖尿病的许多慢性并发症都涉及结缔组织缺陷，如伤口愈合不良、骨形成减少和线性生长减缓。由于胶原蛋白是这些结缔组织的主要蛋白质成分，我们检测了糖尿病大鼠的胶原蛋白生成情况，以此作为结缔组织代谢这一普遍缺陷的研究指标。使用35至300mg/kg剂量的链脲佐菌素诱导大鼠发生代谢严重程度不同的糖尿病。取出顶骨或关节软骨，在37℃下与5微居里的L-[5-³H]脯氨酸一起孵育2小时，用纯化的细菌胶原酶分离后对胶原蛋白和非胶原蛋白生成进行定量。在诱导糖尿病后的2周内，糖尿病大鼠骨骼和软骨中的胶原蛋白生成分别显著降低至对照（注射缓冲液）水平的52%（P＜0.01）和51%（P＜0.01）。相比之下，糖尿病动物骨骼和软骨中的非胶原蛋白生成与对照大鼠组织中的无差异。骨骼（r = -0.77，P＜0.001）和软骨（r = -0.87，P＜0.001）中胶原蛋白相对于总蛋白生成的比例（相对速率）与高血糖程度的相关性都非常显著。发现与胶原蛋白生成改变相关的其他因素包括糖尿病持续时间和体重减轻量。因此，糖尿病与胶原蛋白生成显著减少有关，这在糖尿病诱导后早期即可观察到，并且与非胶原蛋白生成相比具有特异性。胶原蛋白生成这些显著变化的累积效应可能导致糖尿病中的慢性结缔组织并发症。
