Correction of altered collagen metabolism in diabetic animals with insulin therapy

Skeletal abnormalities commonly reported in both human and experimental diabetes include impaired linear growth and osteopenia. In the present study we examined the effect of diabetes and insulin therapy on collagen, the major protein constituent of extracellular matrix. Insulin-deficient diabetes was induced in growing rats by injection of 90 mg/kg of streptozotocin. Articular cartilage and long bone (femur) were removed, and tissues incubated with [3H]-proline in vitro for 2 hours at 37 degrees C. Uptake of [3H]-proline into both collagen and noncollagen proteins was determined using purified bacterial collagenase. In cartilage, collagen production decreased to 46% of buffer-injected control animals within one week of induction of diabetes (p less than 0.01), and remained at this level for three weeks. A similar degree of suppression was found in long bone from untreated animals, in which collagen production decreased to 58% of control (p less than 0.01). Insulin administration at the onset of diabetes prevented the expected decrease in collagen production such that after one week of therapy, collagen production in bone and cartilage was 98% and 93% of control (p +/- 0.01 vs. untreated), respectively. When insulin therapy was delayed for one week after the induction of diabetes, collagen production in articular cartilage increased from 46% to 92% and 97% of control at the end of one and two weeks of therapy (p less than 0.01 vs. untreated), respectively. Noncollagen protein production in untreated rats decreased to 49% of control in long bone and to 72% of control in articular cartilage after one week (p less than 0.01), with correction to control levels in both tissues within one week of insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)