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

Abstract

Summary. Chronic insulin deficiency, in both manand 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 either 14C-6-glucose as a glycolytic marker or 14C-l-glucose as a pentose phosphate pathway marker. While 14C-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. Key words:Chronic insulin deficiency--Epiphyseal growth --Cartilaginous glycolysis --Streptozotocin.Despite numerous reports purporting the coexistence of diabetes mellitus and alterations in bone and mineral metabolism in both man [1][2][3] and the experimental animal [5,6], little is known about the effect of chronic insulin deficiency on the integrity of bone. Clinical studies often have yielded conflicting data [1][2][3][4] and recently, investigators have turned to the alloxan or streptozotocin-treated animal model to gain insight into metabolic and hormonal alterations that may be harmful to skeletal homeostasis.Cartilage growth, matrix synthesis, and subsequent calcification are depende...

Impact of streptozotocin‐induced diabetes on rat blood and alveolar bone affected by occlusal stress

“…On tbe other hand, there was a greater increase in the number of osteoblasts in the control animals than in the diabetic animals. This phenomenon is assumed to be an indication of inhibited osteoblastic activity and bone growth in experimental diabetes (3,4,21). When local artificial stress was omitted, our results from the turnover of alveolar bone were with respect to histologic and biochemical determinations well in agreement \vith the previous studies (4,21,24,26,27).…”

“…duced diabetic animals exhibit h3rpercalcemia, hyperphosphatemia, and striking hypercalciuria and phosphaturia (3,4). Similar but irreversible kinds of symptoms are reported to be present in patients with hyperinsulinemia (5).…”

“…The number of osteoclasts has been reported to diminish significantly (3). Bone turnover is reduced and nortnal skeletal growth is inhibited (3,4,21).…”

Alizarin Red S-Stained Bone and Cartilage in Calcium Deficiency Provoked by Experimental Liver Injury in Rats

“…In the epiphyseal cartilage, chondroitin sulfates are predominant, espe cially in the proliferative zone [Dougherty, 1983], Serum calcium alterations contribute to distrub cartilage metabolism, e.g. in chronic diabetic rats [Hough et al, 1983], In addition, glycolytic activity in the epiphyseal cartilage tissue is changed [Hough et al, 1983], Diffe rent factors could change the appearance of the cartilage in long-term ThAA traumatization. The 'bleached' out look of the bones could simply be a consequence of the extended calcium deficiency due to osteopenia.…”

An Insulinlike Growth Factor I-Resistant State in Cartilage of Diabetic Rats Is Ameliorated by Hypophysectomy: Possible Role of Metabolism

“…The relationship between growth processes, such as cartilage-matrix synthesis, and intracellular metabolism has received little attention (19,20); in particular, little is known about possible changes occurring in IGF-l-mediated processes during IDDM. This study identifies an IGF-I-resistant state in cartilage of growth-arrested IDDM rats, as measured by 35 SO 4 …”