Although changes in collagen production probably play a major role in the connective tissue defects of diabetes, we do not know to what extent these changes are attributable to hormonal/metabolic versus nutritional alterations. To study collagen production as influenced separately by nutrition versus hormonal/metabolic factors, rats were given 50 mg/kg i.v. streptozocin (STZ) (mild weight-gaining diabetes) or 100 mg/kg STZ (severe weight-losing diabetes) and compared with nondiabetic food-restricted rats to match weight changes in diabetic animals. Articular cartilage was incubated with [3H]proline, and uptake of [3H]proline into both collagen and noncollagen proteins was determined with purified bacterial collagenase. Collagen decreased to 49% in mildly diabetic rats and 16% in severely diabetic rats, compared with control rats fed ad libitum and decreased to 85 and 73%, respectively, in food-restricted rats (both P < .01 vs. diabetes). Diabetes induced a greater defect in collagen production than food restriction and a greater decrease in collagen than noncollagen protein production within each group, suggesting a specific effect on collagen. With comparable levels of metabolic severity (glucose, β-hydroxybutyrate), diabetic animals that lost weight produced significantly less collagen than animals that gained weight, suggesting separate mechanisms. Quantitation of the impact of undernutrition on collagen production in diabetes demonstrated that ∼31 to 32% of the defect was due to undernutrition, leaving ∼68–69% of the defect due to the diabetic state. Multivariate analysis of metabolic (glucose, β-hydroxybutyrate), hormonal(insulin, insulinlike growth factor I [IGF-I]), and nutritional (weight change) factors revealed that altered collagen production was correlated only with the degree of weight change (P <.01) in food-restricted animals; reduced collagen production was correlated only with circulating IGF-I (P <.01) in diabetic animals.

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