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

Abstract

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...

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

“…However, other reports have failed to confirm these results and suggested that PTH acts predominantly on the Krebs cycle [35]. Circulating parathyroid hormone is decreased in chronically insulin-deficient rats [6] and significantly increased by dietary calcium restriction, without any appreciable change in immunoreactive insulin [25]. Since cartilage tissue from diabetic animals reared on a low calcium diet demonstrated a significant increase in lactate production with a normalization of glycolysis, it is possible that the defect in glycolytic activity of diabetic rat cartilage may be related to a state of relative hypoparathyroidism.…”

“…Chronically insulinopenic rats maintained elevated plasma calcium levels despite severe hypercalciuria and a pronounced decrease in bone turnover [6]. Diabetic animals reared on a low calcium diet responded with an appropriate increase in plasma iPTH and urinary phosphate excretion [25]. Furthermore, hypercorticosteronism was corrected by calcium restriction in diabetic animals.…”

Changes in the Concentration of Microelements in the Teeth of Rats in the Final Stage of Type 1 Diabetes, with an Absolute Lack of Insulin

“…Probably, an absolute lack of insulin reduces calcium incorporation into the cells and increase concentration of this element in serum [34]. High concentrations of glucagone, probably through the inhibition of alimentary duct motorics, can increase intestinal absorption of calcium and magnesium [35]. Increased levels of calcium through increased levels of calcitonin [34] stimulate estrogen production by increasing the activity of cytochrome P450 aromatase and P450arom gene expression.…”

MECHANISMS IN ENDOCRINOLOGY: Mechanisms and evaluation of bone fragility in type 1 diabetes mellitus

“…Employing short-term (2-week) animal models of streptozotocin diabetes, the low BMD observed in insulinopenic diabetes was earlier explained by secondary hyperparathyroidism and increased bone resorption resulting from a negative calcium balance (impaired intestinal calcium absorption; hypercalciuria) (69,70). Using more appropriate animal models of chronic diabetes (8-10 weeks), and employing time-spaced tetracycline labelled bone histomorphometry, bone formation and resorption were found to be markedly suppressed (71,72,73,74).…”