Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to ascertain whether or not abnormal mineral and vitamin D metabolism in diabetes can be reversed by insulin therapy, plasma calcium, ionized calcium, phosphorus, parathyroid hormone (PTH) and vitamin D metabolites were measured in control, streptozotocin (STZ) diabetic and insulin-treated diabetic rats. Blood glucose levels in diabetic rats treated with insulin decreased to normal. The low plasma calcium and ionized calcium levels in diabetic rats were found to be normal in insulin-treated diabetic rats. An elevated PTH level was observed in the diabetic group, but it was at normal levels in the insulin-treated diabetic group. Plasma 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2D) in the diabetic group were decreased compared to those in control rats, but these were also fully restored to control levels by insulin therapy. However, plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) levels in the untreated diabetic group tended to be lower than in controls, and the values in insulin-treated rats were significantly decreased compared to the control group. The ratio of 1,25(OH)2D to 25(OH)D in diabetic rats was higher than in controls, but it was decreased after insulin therapy and was significantly lower than in the control group. It is suggested, therefore, that the negative calcium balance and decreased 25(OH)D and 24,25(OH)2D levels are derived from the metabolic derangement due to the insulin deficiency. Furthermore, insulin seems to suppress the conversion of 25(OH)D to 1,25(OH)2D in experimental diabetes in vivo.
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PMID:Effects of insulin on altered mineral and vitamin D metabolism in streptozotocin-induced diabetes. 388 88

Previous studies have shown that there is an impairment in renal production of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the major biologically active metabolite of vitamin D3, in diabetes. This impairment is not due to a deficiency in the parathyroid hormone (PTH), a major stimulator of renal 1,25(OH)2D3 production. Therefore, we have investigated the capacity of PTH to stimulate 1,25(OH)2D3 production in insulin deficiency and with insulin replacement. Experiments were performed in rats fed a 0.6% calcium, vitamin D sufficient diet for 2 weeks. Thyroparathyroidectomy was performed on all rats. Rats to be rendered diabetic were injected with streptozotocin immediately after surgery. In non-diabetic rats, PTH administration significantly increased renal 1,25(OH)2D3 production (11 +/- 2 vs 46 +/- 5 pg/min/g; P less than 0.05). In diabetic rats, however, PTH caused only a modest increase in 1,25(OH)2D3 production (11 +/- 1 vs 19 +/- 4 pg/min/g; P less than 0.05). With insulin replacement, PTH stimulation of 1,25(OH)2D3 production was markedly increased over that seen in diabetic rats (48 +/- 12 vs 19 +/- 4 pg/min/g; P less than 0.05). PTH was equally effective in raising serum calcium, depressing serum phosphorus and tubular reabsorption of phosphate in non-diabetic as well as in diabetic rats. These results demonstrate that insulin is necessary for the maximal stimulation of renal 1,25(OH)2D3 production by PTH. However, insulin is not necessary for PTH action in terms of renal handling of phosphate and inducing hypercalcaemia. These results suggest multiple pathways for the action of PTH, only some of which are insulin requiring.
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PMID:Insulin modulates the stimulation of renal 1,25-dihydroxyvitamin D3 production by parathyroid hormone. 389 9

The concentration of 25-hydroxyvitamin D (25(OH)D) was measured in 85 samples of amniotic fluid (AF) obtained near term from mothers with normal pregnancy, diabetes, pre-eclampsia or intrahepatic cholestasis of pregnancy. Significantly lower AF 25(OH)D levels were found in diabetic mothers than in the three other groups. Our results suggest that the vitamin D status of the fetoplacental unit may be somewhat impaired in diabetic pregnancy.
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PMID:Amniotic fluid 25-hydroxyvitamin D concentrations in normal and complicated pregnancy. 395 25

The effect of mild, non-insulin-dependent diabetes (NIDDM) on bone calcification and calcium (Ca) homeostasis was studied in growing rats (males and females). The diabetic state was characterized by mild insulin deficiency, plasma levels being 73% of controls, and mild hyperglycemia, with nonfasting plasma glucose levels of 1.5 times normal. There was no difference in plasma levels of Ca, phosphate (Pi), magnesium (Mg), alkaline phosphatase, immunoreactive parathyroid hormone (iPTH), calcitonin, 25-(OH)vitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2D), and 24,25-dihydroxyvitamin D (24,25[OH]2D) between the NIDDM rats and their controls of either sex. Metabolic Ca and Pi balance studies revealed that the experimental animals of both sexes were in positive Ca and Pi balance similar to that of their controls. Histologic studies of the kidney and intestinal slices from the experimental group were normal. Ca and Pi bone content calculated per gram bone ash of the femur, mandible, and second and fourth caudal vertebrae, and the organic content in the bones of the NIDDM animals showed no difference from their controls. Femur bone density and tibial epiphyseal growth plate width and morphology were similar histologically in the experimental and control rats. No decreased osteoid content in the tibial bone was found in the diabetic rats compared with controls. Physiologic sex differences, consisting of lower plasma Pi, higher plasma calcitonin levels, increased ratio of femur dry bone weight to total body weight, and increased percentage of mineralized and total bone volume at the tibial metaphysis seen in female compared with male control rats were also seen in the diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Apr
PMID:Bone calcification and calcium homeostasis in rats with non-insulin-dependent diabetes induced by streptozocin. 397 85

The first study compared two groups on dialysis: 25 patients with diabetes mellitus and 25 matched non-diabetic patients, in relation to the presence of signs of hyperparathyroidism, to assess the reported low incidence of hyperparathyroidism in these patients. The diabetic group showed significantly lower values of PTH, Alk phosphatase, percentage of patients requiring vitamin D treatment, and less evidence of hyperparathyroidism on X-ray and in bone histomorphometry. In the second study 16 patients with chronic renal failure due to diabetic nephropathy were compared to 27 patients with the same degree of renal failure of other origin, the diabetic nephropathy group showed no increase in PTH, with falling creatinine clearance. Despite this low PTH, the phosphaturia was higher in the diabetic nephropathy group (Tm PO4/C Cr: 1.94 +/- 0.43 vs 2.5 +/- 0.68). In conclusion, patients with diabetes mellitus are less prone to develop hyperparathyroidism in progressive renal failure. This could be due to a relative increase in phosphaturia during declining function.
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PMID:Low incidence of hyperparathyroidism in diabetic renal failure. 399 89

We have previously established the value of 2-dimensional electrophoretic mRNA activity profiles for investigating the hepatic genomic response to several metabolic perturbations, such as thyroid hormone or GH treatment, diabetes, high carbohydrate diet, starvation, and uremia. We now report the effects of adrenalectomy and dexamethasone treatment, and compare these with alterations due to thyroidectomy and T3 treatment. Total rat hepatic RNA was isolated and translated in a reticulocyte lysate system. The [35S]methionine-labeled translated products were separated by 2-dimensional gel electrophoresis and quantified with computerized videodensitometry. Of 200 consistently quantifiable products, 14 (7%) were altered by adrenalectomy and dexamethasone, including 4 products (46, 47, 56, and 57) which have not been observed to change in previous studies from this laboratory. Adrenalectomy increased 5 and decreased 2 products, whereas dexamethasone increased 1 and decreased 8 products. Two products maintained the same directional shift in the transitions form adrenalectomy to control and from control to the dexamethasone-treated state. Thyroidectomy and T3 altered 13 products. Thyroidectomy increased 2 and decreased 7 products, whereas T3 treatment increased 6 and decreased 3 products. Four products maintained the same directional shift in the transitions from thyroidectomy to control and from control to the T3-treated state. In all of the manipulations performed (adrenalectomy, thyroidectomy, dexamethasone treatment, and T3 treatment), a total of 20 separate products changed. One third were affected by alterations of both the steroidal and thyroidal states. However, when adrenalectomy and thyroidectomy were compared, only 7% of the shifts were concordant, whereas 30% of the shifts were concordant when treatment with dexamethasone and T3 were compared. These results demonstrate that the mRNA activity response is highly specific for each hormonal manipulation. In addition, unanticipated interrelationships between steroidal and thyroidal states were observed. In some, the presence of T3 appears necessary for the suppressive effect of dexamethasone. Others show that T3 appears to inhibit a stimulatory effect of dexamethasone. Specificity of response to dexamethasone is emphasized by the lack of response to vitamin D, deoxycorticosterone, and dihydrotestosterone and by a different response to estradiol from dexamethasone.
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PMID:Hepatic messenger ribonucleic acid activity profile of rats subjected to alterations in thyroidal and adrenocortical states: evidence for significant interaction. 399 30

The effect of streptozotocin-induced diabetes on the in vitro conversion of vitamin D3 to 25-hydroxy-vitamin D3 (25-OHD3) by isolated liver microsomes from rachitic rats was examined. Enzymic activity was significantly less than that observed in control animals (P less than 0.001). Administration of insulin restored activity almost to control values. These findings provide evidence that diabetes in this animal model produces alterations in the metabolism of vitamin D.
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PMID:Hepatic metabolism of vitamin D3 in streptozotocin-induced diabetic rat. 624 2

Alterations in circulating vitamin D3 metabolites have been documented in both experimental and human diabetes mellitus. Using a recirculating hepatic perfusion system and in vitro kidney mitochondrial assays, we studied vitamin D3 hydroxylation in control and insulin-deficient rats 6 weeks after the induction of streptozotocin-diabetes. Vitamin D3-25-hydroxylase activity, assessed by hepatic conversion of [3H]vitamin D3 to [3H]25-hydroxyvitamin D3 during a 4-h perfusion, was similar in diabetic and control animals. The hepatic degradation of 25-hydroxyvitamin D3 to more polar metabolites was also normal, as was glucuronide conjugation and biliary excretion of vitamin D3 metabolites. The chronic insulin-deficient state resulted in a significantly (P less than 0.01) decreased 1 alpha-hydroxylase activity and enhanced (P less than 0.001) renal 24-hydroxylase activity. These alterations in vitamin D metabolism may relate to the deranged mineral homeostasis and skeletal morphology observed in rats and humans with chronic insulin deficiency.
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PMID:Vitamin D metabolism in the chronic streptozotocin-induced diabetic rat. 630 55

In order to investigate vitamin D metabolism in insulin-deficient diabetic rats, plasma vitamin D metabolites were measured at various periods after induction of diabetes by iv administration of 60 mg/kg streptozotocin (STZ). After STZ injection, plasma insulin was significantly decreased and plasma urea nitrogen increased with the duration of diabetes, while plasma creatinine remained unchanged. Plasma calcium, 25-dihydroxyvitamin D (25(OH)D), and 24,25-dihydroxyvitamin D (24,25(OH)2D) progressively decreased. On the other hand, plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) did not change at any period, but the ratio of 1,25(OH)2D to 25(OH)D became high in proportion to the severity of hypocalcaemia. Since significantly lower 25(OH)D and 24,25(OH)2D levels were observed at the later stage of diabetes, it is suggested that the altered vitamin D metabolism in diabetes is secondary to the disturbances in metabolic homeostasis derived form the insulin deficiency.
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PMID:Effects of streptozotocin-induced diabetes on circulating levels of vitamin D metabolites. 635 32

Renal calcium binding protein (CaBP), a vitamin D-dependent protein of 28,000 Mr, may be involved in calcium transport by cells of the renal tubule. The streptozotocin-diabetic rat is hypercalciuric and shows markedly decreased concentration of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] in serum and of CaBP in small intestine. To examine the relationship of renal CaBP in diabetes to 1,25-(OH)2D3 and urinary calcium excretion, renal CaBP, serum 1,25-(OH)2D3, and urinary calcium were measured in control, diabetic, and insulin-treated diabetic rats. Treatment of the diabetic rat with insulin decreased urinary calcium excretion and elevated 1,25-(OH)2D3 toward normal. Renal CaBP was found to be the same in controls and diabetics despite a tenfold difference in concentration of 1,25-(OH)2D3 in serum, and to be unaffected by insulin treatment, which elevated 1,25-(OH)2D3 by a factor of 7 above untreated diabetics. It is concluded that in the diabetic rat either (1) the threshold concentration of 1,25-(OH)2D3 for inducing synthesis of renal CaBP is set at a much lower level than that for intestinal CaBP, or (2) since both 1,25-(OH)2D3 and renal CaBP are produced in the kidney, 1,25-(OH)2D3 exerts a paracrine effect on renal CaBP production because of its high local concentration. The increased urinary calcium excretion in the untreated streptozotocin-diabetic rat is not secondary to an alteration in renal CaBP.
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PMID:Diabetes and renal calcium binding protein in the rat. 638 69


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