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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To assess further diabetes-induced alterations in gestational Zn metabolism we examined the uptake/retention and distribution of 65Zn during pregnancy. Control and streptozotocin-induced diabetic rats, with and without insulin treatment, were gavaged with 65Zn on gestational d 12 or 18. Six hours post-intubation, untreated diabetic dams at d 12 of gestation had a lower percentage of retained 65Zn in bone, plasma, erythrocytes, pancreas and spleen than did controls. Retention of 65Zn in amniotic fluid and sacs and in embryos was similar among groups. Untreated diabetic dams at d 18 of gestation had a higher percentage of retained 65Zn in liver, intestine and urine, and most notably a lower percentage in amniotic fluid, placenta, fetus and fetal liver. Lower percentages of 65Zn were found in bone, muscle, plasma, erythrocytes, lung, spleen, heart, pancreas and uterus of diabetic dams compared with controls. HPLC fractionation of samples from maternal livers showed a higher percentage of Zn, Cu and 65Zn associated with the metallothionein peak in samples from untreated diabetic dams compared with other groups, whereas the percentages of Zn, Cu and 65Zn per fraction in fetal liver were similar. The marked decrease in retained 65Zn in products of conception at d 18 suggests either decreased placental transport or altered maternal and/or fetal Zn-binding ligands. Insulin treatment significantly reversed the streptozotocin diabetes-induced derangements in maternal and fetal Zn metabolism.
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PMID:65zinc metabolism is altered during diabetic pregnancy in rats. 152 40

To study the transforming activity of the dbl oncogene and its effect on normal development in vivo, we linked dbl cDNA to promoters with different cell type specificities and used the constructs to generate transgenic mice. The promoters included the mouse alpha A-crystallin promoter, the rat insulin II promoter, and a mouse metallothionein promoter. We also generated transgenic mice carrying a recombinant cosmid clone that contains the entire dbl gene. Mice with the crystallin promoter construct developed cataracts and expressed the dbl protein in their lenses. The architecture of the lenses suggested a block to the normal pattern of differentiation and elongation of the secondary fiber cells. Mice with the insulin II promoter expressed dbl protein in the pancreas but showed no evidence of diabetes and no apparent pancreatic beta-cell defects. Similarly, mice with the metallothionein promoter expressed dbl protein in heart and testes, but showed no pathologic abnormalities in these tissues even after treatment with heavy metals. However, one family of mice carrying the metallothionein promoter construct showed cataracts and a dramatic fibroblastic dysplasia of the lens. One family with the cosmid-dbl gene showed a nearly identical lenticular dysplasia, but with a slower developmental time course. Thus, although the dbl oncogene did not induce neoplasia in any of the mice studied, it is apparently capable of interfering with the ability of the lens epithelial cells to differentiate into lens fiber cells, and of inducing metaplasia of the epithelial cells into fibroblastic cells.
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PMID:Dominant dysplasia of the lens in transgenic mice expressing the dbl oncogene. 206 11

This study was designed to investigate the relationship between the attenuation of cisplatin-induced nephrotoxicity in experimental diabetes and the increased level of renal metallothionein (MT) reported to occur in this condition. Two groups of male Sprague-Dawley rats were used: 42-day streptozotocin diabetics and age-matched nondiabetics. Half of each group was injected with a nephrotoxic dose of cisplatin (5 mg/kg, ip) and half with vehicle. Four hours after injection, renal MT and platinum (Pt) content were quantified. Mean renal MT concentration in vehicle-injected diabetics was about triple that found in nondiabetics. Comparison of renal MT concentrations in cisplatin-injected diabetics and nondiabetics with their vehicle-injected counterparts suggested an inducing effect of the drug. In contrast to the marked elevations of MT in diabetic kidney, mean renal Pt concentration in the cisplatin-injected diabetic group was only about one-fourth that of the nondiabetic group. No difference was evident in the intracellular distribution Pt between cytosolic and particulate fractions from diabetic and nondiabetic kidneys. It was concluded that: (i) Sequestration of Pt by MT cannot account for the resistance of diabetic kidney to cisplatin toxicity. (ii) Rather, the resistance is due to a significant decrease in renal uptake/retention of cisplatin or derivatives during the critical first few hours after injection.
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PMID:Renal metallothionein and platinum levels in diabetic and nondiabetic rats injected with cisplatin. 206 22

The molecular localization of maternal and fetal zinc and copper metalloproteins in diabetic and control rats was studied. Compared to controls, liver and kidneys of diabetic dams showed an increased concentration of zinc and copper that was associated with metallothionein. In contrast, fetuses of diabetic dams had lower zinc and metallothionein levels than fetuses from controls. The abnormal maternal trace element metabolism seen with diabetes resulted in alterations of zinc uptake and/or retention of their fetuses.
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PMID:The effect of diabetes on the molecular localization of maternal and fetal zinc and copper metalloprotein in the rat. 248 70

Diabetic rat pregnancies are characterized by altered maternal and fetal Zn metabolism and a higher frequency of fetal malformations. In this study, the effect of varying maternal dietary Zn on pregnancy and fetal outcome and on maternal and fetal trace element status were investigated. Starting on day 0 of gestation, streptozocin-induced diabetic and nondiabetic control rats were fed a low-Zn diet (4.5 micrograms/g diet), an adequate-Zn diet (24.5 micrograms/g diet), or a high-Zn diet (500 micrograms/g diet) throughout gestation. Fetuses were taken by cesarean section on gestation day 20. Fetuses from diabetic dams were smaller, weighed less, and had less calcified skeletons and more malformations than fetuses from control dams. In the controls, maternal dietary Zn had a minor effect on fetal malformation frequency. In contrast, in the diabetic animals, the low-Zn diet had a strong teratogenic effect. In diabetic dams, the adequate- and high-Zn diets improved fetal length and weight more than it did in fetuses from nondiabetic dams. However, supplemental dietary Zn during diabetic pregnancy did not further improve malformation frequencies. Liver and kidney Zn, Cu, and metallothionein concentrations were higher in diabetic dams than in control dams. In contrast, liver Zn, Cu, and metallothionein concentrations in fetuses of diabetic dams were lower than in fetuses from control dams, regardless of maternal dietary Zn intake. These results show that diabetes during pregnancy can amplify the teratogenic effects of a mild maternal Zn deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1989 Oct
PMID:Influence of maternal dietary Zn intake on expression of diabetes-induced teratogenicity in rats. 279 78

The concentrations of zinc, copper, and manganese in liver, kidney, duodenum, pancreas, testes, bone, and serum from control and untreated, spontaneously diabetic BB Wistar rats were compared. Chronic insulin deficiency resulted in significant alterations in the concentrations of one or more of these essential micronutrients in several tissues. The amounts of zinc and copper bound to metallothionein in the liver and kidney of untreated spontaneously diabetic rats were also markedly increased. The tissue trace metal status in diabetic rats was altered similarly in both male and female rats. Daily injections of insulin blocked many of the changes in the tissue concentrations of the metals. The effects of spontaneous diabetes on tissue trace metal status are quite similar to those reported for chemically induced diabetes. Thus, these results demonstrate that chronic endocrine imbalance is responsible for a series of tissue specific changes in the transport and metabolism of zinc, copper, and manganese.
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PMID:Influence of spontaneous diabetes on tissue status of zinc, copper, and manganese in the BB Wistar rat. 390 Oct 16

The influences of acute and chronic insulin-dependent diabetes on copper and zinc status of liver, kidney, and intestine were investigated in rats at 0-4 wk after streptozotocin (STZ) treatment. The concentration and the tissue contents of copper in liver and kidney were significantly elevated by 1 wk after STZ injection and increased thereafter, attaining levels two- and fivefold higher, respectively, than controls by 4 wk. Increased concentrations of zinc were also present in liver and kidney at 7 and 2 days after treatment, respectively, but zinc accumulated to a lesser degree than copper. In contrast, the concentration of copper and zinc in duodenum from control and all STZ-diabetic groups were similar. Increased and decreased quantities of copper and zinc were bound to metallothionein (MT) in liver and kidney, respectively, within 2 days after STZ injection. Thereafter, the quantities of both metals associated with MT increased with time in both tissues. Additional changes in zinc distribution in hepatic cytosol occurred prior to significant increases in the concentration of this metal in the tissue. The potential significance of altered trace metal metabolism during short-term changes in endocrine status and adverse effects of heavy metal accumulation during chronic hormonal imbalance are discussed.
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PMID:Hepatic and renal metabolism of copper and zinc in the diabetic rat. 682 71

Altered tissue levels of trace metals have been reported in streptozotocin-diabetic (STZ) rats. To determine whether increased hepatic and renal levels of Cu and Zn were associated with enhanced intestinal absorption, trace metal absorption was studied in control (C) and STZ rats using dietary balance and in situ ligated-loop techniques. The apparent daily absorption of dietary Zn and Cu per 100 g body wt was threefold higher in STZ than C rats. In comparison, dietary Fe absorption per day was not altered. Increased Zn absorption was closely correlated with diabetes-associated polyphagia. The initial rate of injected 65Zn excretion was more rapid in STZ rats, although the rate of excretion beyond day 7 was similar from C and STZ animals. The quantity of Zn, Fe, and Cu absorbed per 20 cm duodenal loop was similar for C and STZ rats. Zn, Fe, and Cu absorption per gram dry mucosa were reduced 45-53% in STZ rats due to the 50% increase in mucosal mass. Moreover, the quantity of radioisotopes accumulated per gram dry mucosa and the concentration of metallothionein per gram mucosal cytosol protein were similar in C and STZ animals. Together, these data demonstrate that increased absorption of dietary Zn and Cu is in part responsible for accumulation of these elements in STZ tissues and suggest altered metal transport at the luminal (brush border) surface of the intestinal epithelium.
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PMID:Zinc, iron, and copper absorption in the streptozotocin-diabetic rat. 682 72

Hyperzincuria and low Zn absorption in diabetic animals and humans have prompted speculation that diabetics are more susceptible to Zn deficiency. There is little information, however, describing the effects of diabetes on the biochemical mechanisms of intestinal Zn transport. We evaluated Zn absorption in streptozotocin-induced diabetic rats based on a model of Zn transport in which cysteine-rich intestinal protein serves as an intracellular carrier that is inhibited by metallothionein (MT). Apparent absorption and retention of Zn and Cu in rats fed a purified diet were measured in a balance study 15-17 d after induction of diabetes. The rate of 65Zn absorption from isolated intestinal segments, molecular distribution of 65Zn in mucosal cytosol, and tissue MT levels were measured on d 20-22. Food consumption, and thus Zn and Cu intake, by diabetic rats was twice that of controls. Although fractional absorption (percent) of Zn and Cu was lower in the diabetic rats, net absorption (micrograms/100 g body weight/d) was higher. The higher net absorption in the diabetic group was offset, however, by higher urinary excretion, so that Zn and Cu retention was similar in both groups of animals. Low fractional absorption is attributable to the down-regulation of intestinal Zn transport, as indicated by the lower rate of 65Zn absorption from isolated intestinal segments in the diabetic rats. Down-regulation of intestinal transport is in turn attributable to higher concentrations of intestinal MT, which resulted in more 65Zn in the mucosal cytosol bound to MT, an inhibitor of Zn transport, and less to cysteine-rich intestinal protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of metallothionein and cysteine-rich intestinal protein in the regulation of zinc absorption by diabetic rats. 778 42

Insulin delivery by somatic cell gene therapy was evaluated using murine pituitary AtT20MtIns-1.4 cells. These cells have been stably transfected to release human insulin by the introduction of a recombinant plasmid bearing a human preproinsulin cDNA under the control of a zinc-sensitive metallothionein promoter. 6 x 10(7) AtT20MtIns-1.4 cells were implanted subcutaneously into streptozotocin-diabetic mice immunosuppressed with cyclosporin A. Release of human insulin was assessed using a specific plasma human C-peptide assay. On days 1 and 2 after implantation human C-peptide concentrations were about 0.02 pmol/ml. Consumption of zinc sulphate solution (500 mg/l) as drinking fluid for days 3-5 increased plasma human C-peptide concentrations to 0.11 +/- 0.01 pmol/ml (mean +/- S.E.M.), n = 11, P < 0.01, and concentrations declined when zinc was discontinued. The extent of hyperglycaemia was slightly lower (P < 0.05) than in a group implanted with non-transfected AtT20 cells. The study was terminated after 9 days, and tumour-like aggregations of implanted cells were identified at autopsy. These comprised a large necrotic core with insulin-containing cells at the periphery. The study provides support for the view that somatic cell gene therapy offers a potential approach to insulin delivery in diabetes mellitus.
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PMID:Insulin-releasing pituitary cells as a model for somatic cell gene therapy in diabetes mellitus. 793 Oct 6


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