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)

Diabetes mellitus is a major cause of ischemic coronary artery disease. Endothelial dysfunction is implicated in the pathogenesis of diabetic vascular disease. To examine coronary blood flow (CBF) regulation with endothelium-derived nitric oxide (EDNO) in the diabetic state, we compared the effects of both acetylcholine (ACh) and adenosine (Ado) on left circumflex coronary artery (LCX) blood flow in 12 vehicle-treated and 21 dogs made diabetic with alloxan anesthetized with pentobarbital. All dogs were pretreated with aspirin to inhibit endogenous prostaglandins. None of the hemodynamic parameters were significantly different in the two groups. The percent change in coronary vascular resistance (CVR) after ACh (100 ng/kg) infusion was significantly attenuated in diabetic dogs (-56.5 +/- 1.4%) as compared with vehicle-treated dogs (-64.5 +/- 1.2%) (p < 0.01), whereas the effect of Ado (1 microgram/kg) was not different between the two groups (-71.1 +/- 1.5% in vehicle, -67.0 +/- 1.3% in diabetes). After infusion of incremental doses of NG-nitro-L-arginine methyl ester (L-NAME) 10(-5)-10(-3)M, the effect of ACh was progressively inhibited in both groups and was different no longer between the two groups after the maximal dose. L-Arginine (L-ARG), but not D-ARG, significantly restored the effect of ACh in diabetic dogs but did not affect vehicle-treated dogs. The effect of Ado did not change after L- and D-ARG administration. Cu, Zn-superoxide dismutase (Cu, Zn-SOD) had no effect on any of the effects of ACh and Ado in diabetic dogs. Regulation of CBF with EDNO is impaired in dogs with alloxan-induced diabetes, and this impairment is partially restored by L-ARG.
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PMID:Impairment of coronary blood flow regulation by endothelium-derived nitric oxide in dogs with alloxan-induced diabetes. 879 37

Maternal diabetes during pregnancy is associated with an increased rate of congenital malformations in the offspring. The exact molecular etiology of the disturbed embryogenesis is unknown, but an involvement of radical oxygen species in the teratological process has been suggested. Oxidative damage presupposes an imbalance between the activity of the free oxygen radicals and the antioxidant defence mechanisms on the cellular level. The aim of the present study was to investigate if maternal diabetes in vivo, or high glucose in vitro alters the expression of the free oxygen radical scavenging enzymes superoxide dismutase (CuZnSOD and MnSOD), catalase and glutathione peroxidase in rat embryos during late organogenesis. We studied offspring of normal and diabetic rats on gestational days 11 and 12, and also evaluated day-11 embryos after a 48 hour culture period in 10 mM or 50 mM glucose concentration. Both maternal diabetes and high glucose culture caused growth retardation and increased rate of congenital malformations in the embryos. The CuZnSOD and MnSOD enzymes were expressed on gestational day 11 and both CuZnSOD, MnSOD and catalase were expressed on day 12 with increased concentrations of MnSOD transcripts when challenged by a diabetic milieu. There was a good correlation between mRNA, protein, and activity levels, suggesting that the regulation of these enzymes occurs primarily at the pretranslational level. Maternal diabetes in vivo and high glucose concentration in vitro induced increased MnSOD expression, concomitant with increased total SOD activity, and a tentative decrease in catalase expression and activity in the embryos. These findings support the notion of enhanced oxidative stress in the embryo as an etiologic agent in diabetic teratogenesis.
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PMID:Altered levels of scavenging enzymes in embryos subjected to a diabetic environment. 880 88

The pathogenesis of diabetic corneal epitheliopathy, one of the ocular complications frequently seen in diabetes patients, still remains to be elucidated. Hyperglycemia causes glycation of various proteins leading to the formation of superoxide radicals (O2.-). Copper, zinc-superoxide dismutase (Cu, Zn-SOD), a scavenger of superoxide radicals, whose function is complementary to manganese-SOD (Mn-SOD), is inactivated during glycation. As a first step to clarify whether depressed antioxidant activity is associated with diabetic corneal epitheliopathy or not, we investigated the expression of Mn-SOD mRNA (messenger ribonuclic acid) in streptozotocin-induced diabetic rat cornea by in situ hybridization using a digoxigenin-labeled Mn-SOD cDNA probe. Mn-SOD mRNA was detected in epithelial cell layer and endothelial cell layer of both diabetic rat cornea and normal rat cornea. However, the expression of Mn-SOD mMRA in the epithelial cell layer of diabetic rat cornea was weaker than that of normal rat cornea. These results suggest that decreased Mn-SOD activity might be one of factors causing diabetic corneal epitheliopathy.
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PMID:[Expression of Mn-SOD mRNA in streptozotocin-induced diabetic rat cornea by in situ hybridization]. 881 Feb 35

The concentration of copper ions in cataractous lenses was higher than that in clear lenses. The concentration was significantly higher in the diabetic (DM) group than in the non-diabetic (control) group. Compared to Cu4, the concentration of Cu24 was significantly greater in the DM group. The concentration of protein-unconjugated copper ions was higher than that of protein-conjugated copper ions. I assume that in cataractous lenses of the DM group, decrease of the reactivity of copper-containing enzyme, Cu, Zn-SOD (Cu, Zn-superoxide dismutase), and increase of hydrogen peroxide lead to generation of hydroxyl radicals from a Fenton-like reaction. In diabetes, the increase of lenticular glucose induced glycation and the release of copper ions from copper-containing enzyme, followed by the increase of lenticular copper ions. As a result, superoxide scavenging activity was reduced and peroxide lipid was increased. I assume this to be due to hyperactivity of the cascade of peroxidation.
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PMID:[The association between copper ions and peroxidative reaction in diabetic cataract]. 890 63

1. Oxygen free radicals have been suggested to be a contributory factor in complications of diabetes mellitus. In the present study, we investigated the lipid peroxide level [thiobarbituric acid-reactive substances (TBARS)] and activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) in aorta, heart and blood of control and streptozotocin-induced diabetic rats at various stages of development of diabetes (0 to 6 weeks). 2. There was no change in the TBARS levels of aorta, heart and blood in the control group. A significant (P < 0.05) increase in TBARS levels of aorta, heart and blood was observed in the diabetic group. 3. There were no significant changes in the activities of superoxide dismutase, catalase and glutathione peroxidase in the aorta, heart and blood of control rats at all time intervals. In the diabetic group, there was a significant (P < 0.05) increase in the activity of superoxide dismutase and glutathione peroxidase in aorta from the fourth week onwards while the activity of catalase increased at all time intervals. In the heart of diabetic rats, the activity of total superoxide dismutase and Cu-Zn-superoxide dismutase increased significantly (P < 0.05) from the second week onwards while activity of Mn-superoxide dismutase decreased at the fourth week and increased at the sixth week. The activity of catalase and glutathione peroxidase increased significantly (P < 0.05) at all time intervals. In the blood, the activity of superoxide dismutase and glutathione peroxidase increased from the third week while catalase activity increased from the fourth week. 4. The present findings suggest that oxidative stress starts at early onset of diabetes mellitus and increases progressively.
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PMID:Time course study of oxidative stress in aorta and heart of diabetic rat. 898 69

Exposure to high glucose concentrations increases the mRNA levels of oxygen radical scavenging enzymes in cultured endothelial cells, suggesting a compensatory response to increased free radical production. To test the hypothesis that this response also occurs in vivo, Cu.Zn-superoxide dismutase (Cu.Zn-SOD) and catalase mRNA levels, were measured in the kidneys of Sprague-Dawley rats 17 days after intravenous injection of streptozotocin (60 mg/kg body weight) and compared with those of control rats. Diabetic rats were either left untreated or given differing insulin regimens (2. 3-8, 6-10 IU/day) in two different experiments that were designed to achieve varying degrees of metabolic control. Cu,Zn-SOD and catalase mRNA levels were measured by Northern blot hybridization and standardized by 28S ribosomal RNA determination. Renal Cu,Zn-SOD and catalase mRNA levels were significantly greater in untreated diabetic and in low-dose (2 IU/day) insulin-treated rats than in controls. Treatment with a moderate dose (3-8 IU/day) of insulin normalized catalase but not Cu,Zn-SOD mRNA levels. The highest insulin regimen (6-10 IU/day), in addition to achieving complete metabolic control as evidenced by normal growth and plasma glucose levels, normalized both catalase and Cu,Zn-SOD mRNA levels. Thus, in rats with streptozotocin-induced diabetes Cu,Zn-SOD and catalase renal mRNA levels are greater than in normal rats. This difference is prevented by sufficient insulin dosage to normalize plasma glucose and might be due to an increased production of free radicals.
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PMID:Renal antioxidant enzyme mRNA levels are increased in rats with experimental diabetes mellitus. 902 14

The macrophage product interleukin (IL)-12 is known to drive Th1 reactions in physiological and pathological immune responses. Here we report that treatment with the homodimeric IL-12p40 subunit, an antagonist of the bioactive IL-12p35/p40 heterodimer, suppresses diabetes development in cyclophosphamide-injected NOD mice. Female mice of 70 days old received cyclophosphamide (250 mg/kg) to accelerate and synchronize diabetes development, and daily injections of 1 microgram IL-12(p40)2. While there was no delay of the first diabetes cases, the incidence of overt diabetes was significantly decreased in treated mice (46 vs 23%, p < 0.05). Analysis of mRNA expression in the pancreas showed that administration of the IL-12 antagonist had dampened interferon-gamma gene expression, decreased the ratio of interferon-gamma/IL-10 mRNA levels and in parallel suppressed the expression of the inducible nitric oxide synthase. At the same time intra-islet infiltration was significantly decreased (p < 0.001). Interestingly, the administration of IL-12(p40)2 also affected IL-12 gene expression, by downregulation of p35 mRNA. We conclude that IL-12 p40 homodimer suppresses diabetes development in the NOD mouse by dampening islet inflammation via selective down-regulation of Th1 type responses. The naturally occurring IL-12 antagonist IL-12(p40)2 represents a new and specific Th1 directed approach to prevent autoimmune diabetes.
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PMID:Suppression of cyclophosphamide induced diabetes development and pancreatic Th1 reactivity in NOD mice treated with the interleukin (IL)-12 antagonist IL-12(p40)2. 922 42

The degradation of hyaluronan was followed by viscosimetry and by HPLC in order to study the possible role of Maillard products (lysine-glucose) on the alteration of the vitreous gel in aging and diabetes. Lysine-glucose generated Maillard products produced a decrease of viscosity and of the number average molecular weight (Mn) of hyaluronan during a 1 h incubation at 37 degrees C. This effect was comparable to that produced by 1 U/ml of testicular hyaluronidase but was weaker than the effect of a Fenton-type reagent (Udenfriend's reagent). The polydispersity of hyaluronan incubated with Maillard products appeared higher than with hyaluronidase suggesting a more random reaction. Antioxydant enzymes (SOD, catalase), the iron chelators (desferrioxamine, transferrin) and the free radical scavengers (uric acid, carnosine) inhibited the degradation by Maillard products confirming its free radical nature and the intervention of trace metals. Maillard products have been detected in diabetic vitreous and may play a role in its accelerated modifications (liquefaction) in diabetes as compared to normal aging.
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PMID:Free radical depolymerization of hyaluronan by Maillard reaction products: role in liquefaction of aging vitreous. 951 12

Free radical-mediated damage to vascular cells may be involved in the pathogenesis of diabetic vasculopathy. The aim of this study was to compare the extent of glucose-induced oxidative stress in both vascular smooth muscle cells (VSMCs) and pericytes and the effect on antioxidant enzyme gene expression and activities. Porcine aortic VSMC and retinal pericytes were cultured in either 5 or 25 mmol/l glucose for 10 days. Intracellular malondialdehyde (MDA) was measured as a marker of peroxidative damage, and mRNA expression of CuZn-SOD, MnSOD, catalase, and glutathione peroxidase (GPX) were measured by Northern analysis. Glutathione (GSH) was also measured. There was a significant increase in MDA in VSMCs in 25 mmol/l glucose (1.34 +/- 0.11 vs. 1.88 +/- 0.24 nmol/mg protein, 5 vs. 25 mmol/l D-glucose, mean +/- SE, n = 15, P < 0.01), but not in pericytes (0.38 +/- 0.05 vs. 0.37 +/- 0.05 nmol/mg protein, n = 11). There was a significant decrease in GSH in both cell types (VSMC, 1.40 +/- 0.13 vs. 0.69 +/- 0.12 nmol/mg protein, n = 15, P < 0.001; pericytes, 1.97 +/- 0.17 vs. 0.94 +/- 0.16 nmol/mg protein, n = 11, P < 0.001). mRNA expression of CuZnSOD and MnSOD was increased only in VSMCs (by 58.5 +/- 8.1 and 41.0 +/- 6.9%, respectively, n = 8, P < 0.01). CuZnSOD protein was increased by approximately 120% (P < 0.00001). None of the antioxidant enzyme activities was altered between 5 and 25 mmol/l glucose in either cell type. Both MnSOD activities and GSH concentrations were higher in pericytes compared with VSMC under basal (5 mmol/l) conditions (P < 0.05 and P < 0.02, respectively). These results demonstrate glucose-induced reduction of GSH in both cells, but only in VSMC is there evidence of oxidant damage in the form of lipid peroxidation, implying significant differences in intracellular responses to glucose between contractile cells in the macro- and microvasculature.
Diabetes 1998 May
PMID:Glucose-induced oxidative stress in vascular contractile cells: comparison of aortic smooth muscle cells and retinal pericytes. 958 53

The concentration of copper (Cu) and zinc (Zn) in hair and urine were studied in young nonpregnant healthy women whose both parents were diagnosed for noninsulin-dependent diabetes mellitus (NIDDM descendants) and were compared with those of young healthy nonpregnant females with no family history of NIDDM or hypertension (non-NIDDM descendants) and NIDDM patients. The concentration of Zn in hair in NIDDM descendants was significantly higher than that of non-NIDDM descendants (p < 0.001) and insignificantly higher than that of NIDDM patients. The hair Cu concentrations in NIDDM descendant and patients were significantly lower than that of non-NIDDM descendants (p < 0.001). Hyperzincuria was detected in some NIDDM patients and hypocuperuria in all NIDDM descendants and patients. The data suggest that the young healthy NIDDM descendants possess high-Zn and low-Cu reserves in their bodies, and the observed perturbation appears to be associated with Cu-Zn antagonism.
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PMID:Assessment of copper and zinc status in hair and urine of young women descendants of NIDDM parents. 967 87


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