Spanheimer R G
Department of Medicine, Emory University School of Medicine, Atlanta, GA 30303.
Metabolism. 1988 May;37(5):479-85. doi: 10.1016/0026-0495(88)90050-9.
Diabetes mellitus is associated with a generalized defect in connective tissue metabolism, including decreased growth, poor wound healing, and osteopenia. To determine the role of circulating factors in the etiology of these defects, we studied the effects of diabetic rat serum (DRS) on collagen, the major protein component of connective tissues. After preincubation of costal cartilage from hypophysectomized rats with experimental serum for 20 hours, [3H] proline was added for final four hours of incubation. Collagen and noncollagen protein were quantitated using purified bacterial collagenase. Compared to incubation of tissue in buffer without added serum, collagen production in cartilage incubated with 2% DRS was decreased by 23% (P less than .05), and with 4% serum by 88% (P less than .01). In contrast, serum from normal rats (NRS) increased collagen to 158% above buffer-incubated cartilage at 1.0% (P less than .02) and to 196% at 2% serum (P less than .01). Noncollagen protein production decreased below buffer only after addition of 2% or more DRS and increased above buffer after addition of 2% or more of NRS (178%, P less than .05). Addition of insulin at 10 and 100 mU/mL to DRS did not reverse defective collagen production, and addition of glucose (up to 900 mg/dL) or ketones (20 mmol/L) to NRS did not induce the changes in collagen production seen after addition of diabetic serum. Chromatographic separation of serum revealed that the inhibitory activity of DRS was in the high molecular weight fraction (less than 5000).(ABSTRACT TRUNCATED AT 250 WORDS)
糖尿病与结缔组织代谢的全身性缺陷相关，包括生长减缓、伤口愈合不良和骨质减少。为了确定循环因子在这些缺陷病因中的作用，我们研究了糖尿病大鼠血清（DRS）对胶原蛋白（结缔组织的主要蛋白质成分）的影响。将来自垂体切除大鼠的肋软骨与实验血清预孵育20小时后，在孵育的最后4小时加入[3H]脯氨酸。使用纯化的细菌胶原酶对胶原蛋白和非胶原蛋白进行定量。与在无添加血清的缓冲液中孵育组织相比，用2% DRS孵育的软骨中胶原蛋白产量降低了23%（P小于0.05），用4%血清孵育时降低了88%（P小于0.01）。相比之下，正常大鼠血清（NRS）在1.0%时使胶原蛋白增加至比缓冲液孵育的软骨高158%（P小于0.02），在2%血清时增加至196%（P小于0.01）。仅在加入2%或更多DRS后，非胶原蛋白产量才降至缓冲液水平以下，加入2%或更多NRS后则高于缓冲液水平（178%，P小于0.05）。向DRS中加入10和100 mU/mL的胰岛素并不能逆转有缺陷的胶原蛋白生成，向NRS中加入葡萄糖（高达900 mg/dL）或酮（20 mmol/L）也不会诱导出现加入糖尿病血清后所见的胶原蛋白生成变化。血清的色谱分离显示，DRS的抑制活性存在于高分子量部分（小于5000）。（摘要截短于250字）
