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Regulation of epiphyseal cartilage metabolism and morphology in the chronic diabetic rat

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Summary

Chronic insulin deficiency, in both man and experimental animal models, has been associated with skeletal alterations, the genesis of which remains unknown. Since cartilage growth and maturation are dependent on the maintenance of adequate glycolytic activity, we evaluated cartilaginous carbohydrate metabolism and epiphyseal growth plate morphology in control, long-term (7 weeks) streptozotocin-induced diabetic and insulintreated diabetic rats. Since parathyroid hormone levels have been shown to be decreased in chronically diabetic rats, we also studied the effect of a low calcium diet (0.1%) on cartilage metabolism and morphology in the insulinopenic state.

In vitro incubation of epiphyseal cartilage slices in Kreb's Ringer buffer was performed in 5 mM glucose, with either14C-6-glucose as a glycolytic marker or14C-1-glucose as a pentose phosphate pathway marker. While14C-6-glucose uptake was only marginally reduced in diabetic rat cartilage, lactate production was markedly decreased, approximating 42% of control values, and the activity of the pentose phosphate shunt increased (P<0.01). These biochemical alterations were attended by a marked reduction (P<0.005) in the width of epiphyseal growth plates obtained from rats with untreated diabetes.

Both insulin replacement (P<0.001) and dietary calcium restriction (P<0.02) in diabetic animals resulted in a significant increment in the width of epiphyseal growth plates. These morphologic changes were accompanied by a significant (P<0.02) increase in cartilaginous lactate production, in the absence of altered glucose uptake. While insulin treatment corrected glycolysis, it had little effect on the augmented pentose shunt activity, implying stimulation of both these metabolic pathways. Dietary calcium restriction normalized glycolysis and corrected the accelerated activity of the pentose phosphate pathway.

We conclude that chronic insulin deficiency in the growing rat is attended by alterations in cartilaginous carbohydrate metabolism which may relate not only to insulinopenia per se, but also to the relative hypoparathyroidism that characterizes the chronic experimental diabetic state. The accumulated data also suggest that these metabolic derangements may account, at least in part, for the reduced longitudinal bone growth observed in this growing animal model.

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Authors and Affiliations

  1. Division of Bone and Mineral Metabolism, Department of Medicine, The Jewish Hospital of St. Louis, 216 South Kingshighway, 63110, St. Louis, Missouri

    Stephen Hough, Jean E. Russell, Steven L. Teitelbaum & Louis V. Avioli

  2. Department of Pathology, The Jewish Hospital of St. Louis, 63110, St. Louis, Missouri, USA

    Steven L. Teitelbaum

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  1. Stephen Hough
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  2. Jean E. Russell
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  3. Steven L. Teitelbaum
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  4. Louis V. Avioli
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Hough, S., Russell, J.E., Teitelbaum, S.L. et al. Regulation of epiphyseal cartilage metabolism and morphology in the chronic diabetic rat. Calcif Tissue Int 35, 115–121 (1983). https://doi.org/10.1007/BF02405016

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