Circulating levels and bone contents of bone γ-carboxyglutamic acid-containing protein in rat models of non-insulin-dependent diabetes mellitus

Abstract

Circulating levels and bone contents of bone y-carboxyglutamic acid-containing protein in rat models of noninsulin-dependent diabetes mellitus. Acta Endocrinol 1993;128:69-73. ISSN 0001-5598 In order to investigate the pathophysiology of the diabetic osteopenia observed in non-insulin\x=req-\ dependent diabetes mellitus, the circulating levels and the bone contents of bone \g=g\-carboxyglutamic acid-containing protein (osteocalcin) were determined in rat models of non-insulin-dependent diabetes mellitus, neonatally streptozotocin-induced rats and in genetic Wistar fatty rats. In Wistar fatty rats the plasma level of osteocalcin was 8.1 \m=+-\0.8nmol/l, significantly lower than the value of 1 7.3 \m=+-\0.9nmol/l in their lean littermates (p < 0.001). Bone length, bone strength, and weight of powdered bone in Wistar fatty rats were significantly decreased compared to control rats (p<0.001, p<0.02 and p<0.001, respectively). Bone content of osteocalcin per femur in Wistar fatty rats was also significantly decreased compared to controls (p<0.001). In addition, plasma osteocalcin in neonatally streptozotocin-induced diabetic rats was 2.9\m=+-\0.3nmol/l, which was also significantly decreased compared to the value of 5.6\m=+-\0.5nmol/l in their controls (p<0.001). Since it has been established that the plasma level of osteocalcin is well related to bone formation and turnover, the low plasma values in these animal models suggest that bone formation and turnover are decreased in non-insulin-dependent diabetes mellitus. Low bone formation and turnover are, therefore, postulated to be one of the pathophysiological characteristics of the skeletal tissue in non-insulin-dependent diabetes mellitus, and to be at least in part responsible for the occurrence of this complication. Diabetic osteopenia has been recognized as one of the chronic complications of diabetes mellitus in patients with insulin-dependent diabetes mellitus (1-3) and in those with non-insulin-dependent diabetes mellitus (1, 4, 5). Although a negative calcium balance has been suggested to be characteristic of the diabetic state (3, 6) and altered mineral and vitamin D metabolism has been found to be associated with this complication (5, 7, 8), the exact mechanism responsible for the pathogenesis of diabetic osteopenia remains unclear.Bone y-carboxyglutamic acid-containing protein (osteocalcin) has been shown to be one of the major noncollagenous proteins in the extracellular bone matrix (9, 10). Recent studies have revealed that calcitriol stimu¬ lates osteocalcin synthesis in osteoblastic cells (11), and plasma osteocalcin levels have been found to be a sensitive marker for bone formation and turnover in patients with metabolic bone diseases (12). We have previously reported that both circulating levels and bone contents of osteocalcin are significantly decreased in streptozotocin (STZ)-induced insulin-dependent diabetic rats, which have the complication of osteopenia (13). Since decreased plasma osteocalcin levels have been similarly observed in human and...

Effects of streptozotocin-induced diabetes mellitus on some bone turnover markers in the vertebrae of ovary-intact and ovariectomized adult rats

“…Similarly, decreased breaking strength was found at the femoral neck of STZ diabetic rats, which was partly restored by insulin treatment (Hou et al 1993). Femoral breaking strength was also found to be decreased in models of type-2 diabetes (Takeshita et al 1993). As in human diabetics, fracture repair is delayed in diabetic rats, as evidenced by the lower callus volume and BMC after fracture of the fibula in STZ diabetic rats compared with that in nondiabetic rats (Kawaguchi et al 1994).…”

Characteristics of bone turnover, bone mass and bone strength in Spontaneously Diabetic Torii-Lepr fa rats

“…In addition, obesity impaired bone formation and decreased bone mass in growing rats [22]. Wistar fatty rats, an obese type 2 diabetes model rat, showed shortening of bone length, and decreases in osteocalcin and bone calcium content in the femur [23]. Based on these data, it is considered that hyperglycemia-and obesity-induced low bone formation in SDT-fa/fa rats causes severe bone loss, shortening of bone length, deterioration in bone geometrical properties, and consequently decreased bone strength.…”

Possible compensatory role of parathyroid hormone-related peptide on maintenance of calcium homeostasis in patients with non-insulin-dependent diabetes mellitus

“…The corrections for urine PTHrP and albumin concentrations were performed by the division of these values by the urinary creatinine levels. The severity of diabetic nephropathy was defined as without nephropathy, microalbuminuria and macroproteinuria, when the corrected values of urinary albumin concentration were less than 30 g/kg creatinine, between 30 and 300 g/kg creatinine and more than 300 g/kg creatinine, respectively. Statistical comparisons of means between groups were performed using Student's unpaired £-test.…”