The Effects of Colchicine and Vinblastine on Parathyroid Hormone Secretion in the Rat

Chanard, J; Black, Robert H.; Purkerson, Mabel L.; Lewis, Jr. James S.; Klahr, Saulo; Slatopolsky, Eduardo

doi:10.1210/endo-101-6-1792

Cited by 32 publications

(11 citation statements)

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“…Plasma levels of insulin (28), corticosterone (29), calcitonin (30) and PTH (31) were determined by RIA. The PTH antiserum was specific for the carboxyl-terminal.…”

Section: Methodsmentioning

confidence: 99%

Correction of Abnormal Bone and Mineral Metabolism in Chronic Streptozotocin-Induced Diabetes Mellitus in the Rat by Insulin Therapy*

et al. 1981

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Mineral homestasis and skeletal morphology were studied in freely fed control, streptozotocin-induced diabetic, and insulin-treated diabetic rats 7 weeks after the induction of diabetes. The untreated diabetic animals were characterized by modest hypercalcemia, hyperphosphatemia, and striking hypercalciuria and phosphaturia. Insulin treatment corrected the hypercalcemia and markedly reduced the calciuria (P < 0.001), but had no significant effect on the urinary phosphate levels. Circulating immunoreactive parathyroid hormone (iPTH) was detectable in only 6% of untreated diabetic animals compared to 30% of controls. Furthermore, in untreated diabetic animals, the circulating levels of iPTH, when detectable, approximated the lower limits of the assay. The urinary cAMP levels of untreated diabetic animals were markedly decreased. Both iPTH and urinary cAMP approximated control levels in insulin-treated rats. Conversely, plasma immunoreactive calcitonin was increased in the diabetic rats compared to control animals (P < 0.001) and was partially corrected by insulin treatment (P < 0.05). Plasma corticosterone was elevated 10-fold in the untreated diabetic rats and was not significantly influenced by insulin therapy.The bone histology of the diabetic animals reflected the biochemical changes. Parameters of skeletal turnover, notably the quantity of nonmineralized bone matrix, reflecting boneforming sites (P < 0.01), and the numbers of osteoclasts (P < 0.025), were significantly diminished in the diabetic animal. Furthermore, diabetic vertebrae failed to assume a tetracycline label. Biochemical parameters of bone turnover, namely skeletal alkaline phosphatase activity and urinary hydroxyproline excretion, were likewise decreased. Untreated diabetes resulted in growth arrest, as evidenced by a significant reduction (P < 0.005) in the width of the epiphyseal growth plate. Insulin therapy in these chronically diabetic rats resulted in the normalization of all histometric parameters of skeletal turnover and growth.We conclude that prolonged streptozotocin-induced diabetes mellitus in the rat results in reduced bone turnover and growth arrest, which are completely corrected by insulin therapy. Whether this response to therapy reflects a direct insulin effect on skeletal tissue or results from the associated correction of mineral derangements and decreased PTH secretion which characterize the chronic experimental diabetic state remains to be resolved. (Endocrinology 108: 2228, 1981) T HE COEXISTENCE of diabetes meUitus and altered bone and mineral metabolism has been established by a number of investigators both in diabetic patients and in animals with experimentally induced insulin deficiency syndromes (1-5). However, the pathogenesis of these alterations, their natural evolution, and their response to therapy remain ill defined. Earlier clinical studies implicated poor metabolic control, ketoacidosis, and nutritional deprivation (1), but recent reports indicate that skeletal derangements in diabetes are not

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“…Plasma levels of insulin (28), corticosterone (29), calcitonin (30) and PTH (31) were determined by RIA. The PTH antiserum was specific for the carboxyl-terminal.…”

Section: Methodsmentioning

confidence: 99%

Correction of Abnormal Bone and Mineral Metabolism in Chronic Streptozotocin-Induced Diabetes Mellitus in the Rat by Insulin Therapy*

et al. 1981

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“…Animals, 8-12 from each of the four subgroups, were sacrificed on the 48th day (08 OOh-10 OOh) after a 6-8 h fast, by exsanguination from the abdominal aorta under light ether anesthesia. Serum glucose [9], calcium [10], phosphate [11], insulin [12], and corticosterone [13] were measured; immunoreactive parathyroid hormone was determined by a carboxy-terminal assay [14]. Prior to sacrifice, two 24-h urine collections were made for glucose [9], calcium [10], and phosphate [11] determinations.…”

Section: Methodsmentioning

confidence: 99%

Hormonal alterations in experimental diabetes: Role of a primary disturbance in calcium homeostasis

1983

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Summary. Chronic diabetes mellitus in the rat isattended by a reduced bone turnover and growth arrest, decreased circulating immunoreactive parathyroid hormone (iPTH), and hypercorticosteronism. Since chronic insulin deficiency in the rat is associated with intestinal hyperabsorption of calcium and a positive calcium balance that may account for the decreased iPTH, as well as other hormonal alterations observed in these animals, we studied the effect of long-term (5 week) dietary calcium restriction (0.1% Ca, 0.8% P) in control and streptozotocin-induced diabetic rats. Chronic diabetic rats reared on a normal calcium (1.2% Ca) diet had increased serum calcium and phosphate (Pi) concentrations and were markedly hypercalciuric and phosphaturic compared with controls. Serum corticosterone was increased and iPTH markedly decreased in the diabetic animals.Dietary Ca restriction (0.1% Ca) decreased urinary calcium excretion and resulted in a comparable phosphaturic response in both control and diabetic rats. Moreover, although Ca restriction in diabetic animals had no appreciable effect on serum insulin, serum glucose, or urinary glucose excretion, it was associated with a marked increase in circulating iPTH: this resulted in serum concentrations comparable with that observed in control animals reared on the low Ca diet. These results support the hypothesis that the decreased circulating iPTH observed in chronic diabetic rats results predominantly from their intestinal hyperabsorption of Ca. In contrast to control animals, diabetic rats reared on a low Ca diet failed to maintain their serum Ca despite the marked increase in serum iPTH and striking decrease in calciuria, thus underscoring the reliance of these animals on intestinal hyperabsorption of Ca to maintain Ca balance under conditions of adequate Ca intake. Serum corticosterone was insignificantly altered by dietary Ca restriction in control rats; hypercorticosteronism, characteristically observed in diabetic rats, was normalized by Ca restriction. We conclude that a primary disturbance in Ca homeostasis may contribute, in part, to hormonal alterations observed in chronic experimental diabetes. Key words:Chronic insulin deficiency --Hypercorticosteronism --Dietary calcium restriction --Streptozotocin-induced.Insulin deficiency in both man [1][2][3] and experimental animal [4,5] is attended by alterations of bone and mineral metabolism. We have recently documented that chronic insulin deficiency in the rat results in reduced bone turnover and growth arrest, decreased plasma iPTH levels, and hypercorticosteronism [4]. The pathogenesis of these alterations, and specifically, their relationship to insulinopenia per se is, however, still conjectural.Chronically diabetic rats reared on a nutritionally adequate diet maintain normal to frankly elevated plasma Ca levels, through augmented intestinal absorption of Ca, despite severe hypercalciuria and a pronounced decrease in bone turnover [4,5]. Since the intestinal hyperabsorption of Ca and the positive Ca balance obser...

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“…Parathyroid hormone levels were determined with a carboxyterminal assay as previously described (20). Probabilities of' difference were calculated with the paired t test.…”

Section: Methodsmentioning

confidence: 99%

Lithium inhibition of bone mineralization and osteoid formation.

Baran¹,

Schwartz²,

Bergfeld³

et al. 1978

J. Clin. Invest.

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A B S T R A C T Lithium chloride administration to growing rats, which resulted in circulating lithium levels of 1.4 meq/liter, was attended by significant suppression of bone mineralization and organic matrix synthesis as assessed by tetracycline labeling and histological quantitation of osteoid, respectively. These effects of lithium were not associated with changes in animal behavior, nor were there any significant differences in blood levels of calcium, phosphorus, alkaline phosphatase, creatinine, pH, or parathyroid hormone. The data suggest that lithium inhibition of bone mineralization is secondary to suppression of osteoid formation.

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The Effects of Colchicine and Vinblastine on Parathyroid Hormone Secretion in the Rat

Cited by 32 publications

References 0 publications

Correction of Abnormal Bone and Mineral Metabolism in Chronic Streptozotocin-Induced Diabetes Mellitus in the Rat by Insulin Therapy*

Correction of Abnormal Bone and Mineral Metabolism in Chronic Streptozotocin-Induced Diabetes Mellitus in the Rat by Insulin Therapy*

Hormonal alterations in experimental diabetes: Role of a primary disturbance in calcium homeostasis

Lithium inhibition of bone mineralization and osteoid formation.

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