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 hagfish islet parenchyma, consisting practically only of insulin-producing B-cells and agranular B-cell precursors, the contents of glutathione (GSH) and total protein-free thiols (NPSH) were determined on micro-dissected islet lobules. GSH was found to be of the same order of magnitude (22-25 mg/100 g wet weight) as in the islet parenchyma of a previously studied teleost fish and of some mammals, including man. However, the NPSH was found to be considerably higher in the islet lobules of the hagfish than in the teleostean islet parachyma. As in both teleost fish and mammals, GSH made up most of the NPSH in the hagfish erythrocytes, myocardium, and skeletal musculature. This discrepancy between hagfish islet parenchyma and other tissues indicates that the non-GSH portion of NPSH may be of particular significance for the insulin-producing B-cells. By means of flameless atomic absorption spectrophotometry the contents of zinc, cobalt, and manganese were determined in micro-dissected hagfish islet lobules. Neither zinc, nor cobalt, occurred in significantly higher concentrations in the islet parenchyma than in the liver or the skeletal musculature. Only manganese was found in somewhat higher amounts in the islet lobules than in the other tissues, but the contents were still low. The results indicate that none of the three heavy metals play any important role in the synthesis, storage, or release of insulin in the hagfish. The significance of this in relation to the prevailing hypotheses regarding the pathogenesis of alloxan diabetes is discussed.
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PMID:Microchemical assays of glutathione, zinc, cobalt and manganese in micro-dissected areas of the endocrine pancreas in the hagfish, Myxine glutinosa. 33 56

The intravenous injection of zinc or manganese chloride immediately before and 15 minutes after alloxan or dithizone prevented the usual hyperglycemia observed 24 hours after induction of diabetes. Injection of zinc chloride in alloxan diabetes led to normalization of sodium while zinc, copper, iron and magnesium remained high and calcium and potassium remained low as in alloxan. In case of dithizone diabetes, the administration of zinc salt led to an increase in serum zinc, magnesium and potassium and to a decrease in serum calcium while the sodium level returned to normal. Manganese plus alloxan led to a normalization of serum zinc, copper, potassium and sodium. In the case of dithizone plus manganese only magnesium was raised while the other elements were unchanged when compared to animals injected with dithizone only. Chromium and cobalt lowered the blood glucose to a certain extent however it did not affect most of the elements. The same changes occurred in all elements as with alloxan or dithizone alone. Pretreatment with ATP led to a normalization of serum zinc, copper, magnesium, sodium and potassium, while in case of iron it remained high and calcium remained low as that found in alloxan diabetic rats.
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PMID:Serum mineral changes due to exogenous ATP and certain trace elements in experimental diabetes. 44 5

Interactions between manganese (Mn) deficiency and streptozotocin (STZ)-diabetes with respect to tissue antioxidant status were investigated in male, Sprague-Dawley rats. All rats were fed either a Mn-deficient (1 ppm) or a Mn-sufficient (45 ppm) diet for 8 wk. Diabetes was then induced by tail-vein injection of STZ (60 mg/kg body weight), after which the rats were kept for an additional 4 or 8 wk. The control groups comprised rats not injected with STZ and fed either Mn-deficient or Mn-sufficient diets for a total of 12 wk. The Mn-deficient diet decreased the activities of manganese superoxide dismutase (MnSOD) in kidney and heart, and of copper-zinc superoxide dismutase (CuZnSOD) in kidney, in the non-diabetic animals. In the diabetic rats, the Mn-deficient diet induced more pronounced decreases in activities of these same enzymes, and also increased liver MnSOD activity. Plasma and hepatic vitamin E levels increased progressively with the duration of diabetes, independent of dietary Mn intake. Lipid peroxidation, as measured by H2O2-induced production of thiobarbituric acid reactive substances in erythrocytes, also increased, concomitant with decreased liver and kidney glutathione (GSH) levels. These findings demonstrate for the first time and interactive effective between Mn deficiency and STZ-diabetes, resulting in amplification of tissue antioxidant changes seen with either Mn deficiency or STZ-diabetes alone. This effect of Mn deprivation in experimental diabetes suggests a physiological role for Mn as an antioxidant nutrient.
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PMID:Tissue antioxidant status in streptozotocin-induced diabetes in rats. Effects of dietary manganese deficiency. 128 89

The 2.2 A resolution crystal structure of recombinant human manganese superoxide dismutase, a homotetrameric enzyme that protects mitochondria against oxygen-mediated free radical damage, has been determined. Within each subunit, both the N-terminal helical hairpin and C-terminal alpha/beta domains contribute ligands to the catalytic manganese site. Two identical 4-helix bundles, symmetrically assembled from the N-terminal helical hairpins, form novel tetrameric interfaces that stabilize the active sites. Structurally altered polymorphic variants with reduced activity, such as tetrameric interface mutant Ile-58 to Thr, may produce not only an early selective advantage, through enhanced cytotoxicity of tumor necrosis factor for virus-infected cells, but also detrimental effects from increased mitochondrial oxidative damage, contributing to degenerative conditions, including diabetes, aging, and Parkinson's and Alzheimer's diseases.
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PMID:The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles. 139 26

1. Decreased beta-adrenergic and serotonergic responses have been reported in gastro-intestinal tract of experimentally diabetic rats. Effects of lithium on the decreased beta-adrenergic and serotonergic responsiveness of the gastro-intestinal tract due to diabetes were investigated using gastric fundus strips and proximal duodenum from alloxan diabetic rats. 2. A 6-day treatment with lithium chloride (2 mEq/kg i.p. in saline) normalized the decreased gastro-intestinal responses of the alloxan-diabetic rats, whereas the lithium treatment did not affect the elevated blood glucose levels due to experimental diabetes. 3. Furthermore, the lithium treatments of control and alloxan-diabetic rats did not alter the relaxing effect of manganese chloride on the isolated duodenum. 4. These results strongly suggest that the improving effect of lithium is not related to adenylate cyclase activation and may be as a consequence of its direct action on the diabetic gastro-intestinal smooth muscles.
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PMID:Effect of lithium on gastro-intestinal complications in alloxan-diabetic rats. 139 84

Studies from several laboratories suggest that oxidized LDL may play an important role in atherogenesis. Our group previously showed that treatment of aortic endothelial cells with low levels of MM-LDL caused increased expression of MCP-1, M-CSF, tissue factor, and a monocyte-binding protein. In these studies MM-LDL was produced by storage of native LDL. We now show that cocultures of endothelial and smooth muscle cells can also produce MM-LDL from native LDL. This production of MM-LDL by cells is prevented by preincubating the LDL with probucol or vitamin E. However, addition of antioxidants to MM-LDL did not block its action. In past studies we also showed that endothelial cells exhibit differential sensitivity to the effects of MM-LDL. We report herein that in resistant cells there is no elevation of catalase, glutathione peroxidase, or copper-zinc-dependent SOD. However, manganese-dependent SOD is elevated in resistant cells. Ways in which MM-LDL production may be elevated in poorly controlled diabetics subjects are discussed.
Diabetes 1992 Oct
PMID:Minimally modified lipoproteins in diabetes. 152 40

The degradation of native and 125I-labeled human insulin (HI) was examined in the cytosolic fraction of human, monkey, and rat liver. The purpose of these studies was to provide a species comparison of the interaction of insulin-degrading enzyme (IDE) and protein disulfide isomerase (PDI) in the degradation of HI. Western-blot analysis with monoclonal antibodies indicated the presence of both IDE and PDI in the cytosolic fraction of human and monkey liver. In contrast, rat liver cytosol contained, detectable levels of IDE only. A species comparison of metabolic profiles was performed by fractionating peptide products with reversed-phase high-performance liquid chromatography. After a 60-min incubation, human liver cytosol degraded unlabeled HI into three major products. Two of these peptides coeluted with the products of the incubation of HI with purified rat liver PDI. The three peptides were isolated and determined by NH2-terminal sequence analysis to be intact A chain, B chain, and des(Phe1)-B chain. Human liver cytosol also formed 125I-A chain and 125I-B chain as major products when specifically labeled 125I-HI isomers were used as substrate. Significant proteolytic degradation was observed only when reactions with human liver cytosol were supplemented with Mn2+. In contrast, monkey and rat liver cytosol proteolytically degraded 125I-HI isomers to small peptide fragments. The rat and monkey metabolic profiles were similar to each other and to that observed with Mn(2+)-supplemented human liver cytosol. Proteolysis in monkey and rat was sensitive to inhibition by EDTA.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Apr
PMID:Mechanisms involved in degradation of human insulin by cytosolic fractions of human, monkey, and rat liver. 160 78

Rat liver microsomes contain type-1 S6 phosphatase (acting on the serine residues phosphorylated by protein kinase A) and type-1 phosphorylase phosphatase activities. The main aim of this study has been to characterize the microsomal S6 phosphatase activity and to compare its properties with those of the phosphorylase phosphatase activity in the same microsomal preparation. The specific activities of both microsomal S6 phosphatase and phosphorylase phosphatase were 1.6- to 1.7-fold higher in the smooth endoplasmic reticulum than in the rough sarcoplasmic reticulum. Both phosphatase activities were inhibited to a similar extent by MgCl2 (10 mM) and NaF (22 mM), were completely suppressed by glycerophosphate (80 mM) and ZnCl2(10 mM), and were stimulated by MnCl2(1 mM). When analyzed by gel filtration on Sephadex G-100 superfine, both phosphatase activities eluted as broad peaks, stretching from the void volume to 45-60 kDa. The microsomal S6 phosphatase and phosphorylase phosphatase activities also displayed the following distinct characteristics: (a) Mn2+ stimulated the S6 phosphatase activity 2.9-fold more than the phosphorylase phosphatase activity, (b) limited trypsin digestion of microsomal preparations increased the phosphorylase phosphatase activity by 1.5- to 2-fold, but decreased the S6 phosphatase activity by 50%, (c) a synthetic peptide analog of S6 (S6229-239) (200 microM), which did not act as a substrate for the microsomal S6 phosphatase and did not affect its activity, inhibited the microsomal phosphorylase phosphatase activity by about 50%, and (d) the elution profile of the phosphorylase phosphatase activity was markedly broader than that of the S6 phosphatase activity. A series of in vivo studies showed that streptozotocin-diabetes and insulin replacement therapy as well as ip injection of insulin or vanadate, which modified the microsomal S6 phosphatase activity, had no statistically significant effects on the microsomal phosphorylase phosphatase activity. Taken together, these results suggest that the microsomal S6 phosphatase and phosphorylase phosphatase activities are due to two distinct enzyme populations.
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PMID:A comparative study of the microsomal S6 phosphatase and phosphorylase phosphatase activities in rat liver. 165 55

Dietary boron, in concentrations similar to that found in human diets comprised mainly of fruits and vegetables, affects both mineral and energy metabolism. Therefore, the effects of boron on a model system with a perturbed metabolic insulin-vitamin D3 axis was examined. Weanling male rats were fed a ground corn-high protein casein-corn oil-based diet (0.06 mg B/kg; no supplemental vitamin D3) supplemented with B (as orthoboric acid) at 0 or 2.4 mg/kg. After 55 days, all rats were equilibrated in individual metabolic cages for 6 days. After another 6 days, one half of the rats in both dietary groups were injected intraperitoneally with streptozotocin (STZ). All rats were killed 3 days after STZ treatment. STZ affected many aspects of mineral metabolism as expected. Plasma ionized calcium concentrations fell by approximately 10% in STZ-treated rats. Brain and heart mineral metabolism was spared from the toxic effects of STZ whereas spleen mineral metabolism was especially vulnerable to STZ. Supplemental dietary boron increased urinary excretion of calcium in the non-STZ rats but did not affect the plasma concentrations of alkaline phosphatase, ionized calcium or the concentration of calcium in the brains, lungs, kidneys and spleens of those animals. Supplemental dietary boron temporarily reduced the abnormally elevated renal excretion of albumin, potassium and sodium during the acute phase of diabetes mellitus. On the other hand, physiological amounts of dietary boron exacerbated the abnormally elevated rate of collagen breakdown in the STZ animal. Finally, boron may have indirectly affected heart mineral metabolism because dietary boron did not affect cardiac boron concentrations but did affect cardiac copper, calcium, manganese, molybdenum and phosphorus concentrations, primarily in non-STZ rats. The findings suggest that dietary boron has both protective and regulatory roles in mineral metabolism.
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PMID:Effects of dietary boron on calcium and mineral metabolism in the streptozotocin-injected, vitamin D3-deprived rat. 166 22

The urinary excretion of chromium, copper and manganese was determined in 185 diabetics and in an equal number of control subjects by measuring the concentration of each of these metals using electrothermal atomic spectrophotometry and dividing the values by the urinary concentration of creatinine (creat) in each subject. The mean (SEM) values for the overall diabetics and the control group were 2.32 (0.17) and 2.62 (0.22) mumol Cr/mole of creat, 76.5 (5.5) and 73.9 (6.1) mumol Cu/mole of creat, and 3.56 (0.44) and 2.66 (0.3) mumol Mn/mole of creat, respectively. There was no correlation between the urinary excretion of any of the metals examined and age or sex of either group. While the cardiovascular or ophthalmologic diseases associated with diabetes did not influence the excretion of any of these metals, significantly higher urinary excretion of Cu was exhibited by diabetics with neuropathy (p < 0.0027) or infections (p < 0.014) than by those without. Also, diabetics with liver disorders or those who were not treated with insulin excreted significantly more Mn than did their diabetic counterparts.
Diabetes Res 1991 Nov
PMID:Urinary excretion of chromium, copper, and manganese in diabetes mellitus and associated disorders. 184 23


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