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)

Microbial enzymes were studied from two medicinal viewpoints. First, we examined proline-specific peptidases from pathogenic microorganisms. We found several proline-specific peptidases in pathogenic bacteria. Among them, prolyl tripeptidyl aminopeptidase from Porphylomonas gingivals and prolyl aminopeptidase from Serratia marcescens were crystallized. The complex structures of those enzymes and inhibitors were clarified in X-ray crystallography. Aminopeptidase N, which has wide specificity for amino acids, was distributed in the pathogens. The crystal structure of the aminopeptidase N elucidated the reasons for its wide substrate specificity but inertness to the X-Pro bond. It was also revealed that proline-specific peptidases and aminopeptidase N cooperatively degrade collagen for the uptake of amino acids as nutrition when these bacteria infect cells. Second, we applied enzymes from microorganisms to diagnostic analyses. We found a series of creatinine-metabolizing enzymes in Pseudomonas putida. Creatininase, creatinase, and sarcosine oxidase were coupled and have been developed for a diagnostic analysis kit that examines renal function. The structures of the native and the Mn2+-activated creatininases were determined in X-ray crystallography. Based on the structure, the activated enzyme was used for an improved assay kit. The structure of D-3-hydroxybutyrate dehydrogenase from Pseudomonas fragi was also clarified in crystallography. The enzyme is useful for diagnostic analysis of diabetes mellitus while monitoring ketone bodies.
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PMID:[Biochemistry and structural biology of microbial enzymes and their medical applications]. 1760 62

Oxidative stress is an important component of diabetes and its complications. Manganese (Mn), the key component of the Mitochondrial antioxidant (MnSOD), plays a key role in the superoxide uncoupling protein 2 (UCP-2) pathway in inhibiting of glucose-stimulated insulin secretion (GSIS). The interactions of Mn with ascorbate and other components of this pathway have not been defined in type-2 diabetes. Fifty established type 2 diabetics (30 males, 20 females) and 30 non-diabetics (controls; 18 males, 12 females) matched for age and sex were investigated. Dietary intake, particularly of micronutrients as assessed by 24-h dietary recall was similar between diabetics and controls. Weight and height of all subjects were determined and body mass index (BMI) computed after clinical assessment. Fasting plasma glucose, manganese, ascorbic acid, creatinine and K+ levels were determined; K+ was to assess the K+ channels, whereas creatinine was to assess probability of oxidative stress nephropathy. Body mass index was greater in DM than in controls (p < 0.001). Fasting plasma glucose and Mn levels (p < 0.00 and p < 0.01, respectively) were higher in diabetes than in the controls. Manganese level was greater than twice the levels in controls. Ascorbic acid was not significantly different (p > 0.05), but was 50% lower than the level in non-diabetics. Potassium like Mn and glucose was significantly higher in diabetes mellitus (DM) than in controls (p < 0.001). Creatinine was not significantly different between diabetics and controls (p > 0.05). Correlations among all parameters were not significantly different. These findings suggest absence of significant oxidative stress in the mitochondria, probably excluding a role for UCP-2-superoxide pathway in the inhibition of glucose-stimulated insulin secretion (GSIS), calling for caution in the precocious conclusion that interruption of UCP-2 activity may provide a viable strategy to improve beta-cell dysfunction in type 2 diabetes mellitus.
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PMID:Increased plasma manganese, partially reduced ascorbate, 1 and absence of mitochondrial oxidative stress in type 2 diabetes mellitus: implications for the superoxide uncoupling protein 2 (UCP-2) pathway. 1791 51

There is accumulating evidence that the metabolism of several trace elements is altered in diabetes mellitus and that these nutrients might have specific roles in the pathogenesis and progress of this disease. The aim of present study was to compare the level of essential trace elements, chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), and zinc (Zn) in biological samples (whole blood, urine, and scalp hair) of patients who have diabetes mellitus type 2 (n = 257), with those of nondiabetic control subjects (n = 166), age ranged (45-75) of both genders. The element concentrations were measured by means of an atomic absorption spectrophotometer after microwave-induced acid digestion. The validity and accuracy was checked by conventional wet-acid-digestion method and using certified reference materials. The overall recoveries of all elements were found in the range of (97.60-99.49%) of certified values. The results of this study showed that the mean values of Zn, Mn, and Cr were significantly reduced in blood and scalp-hair samples of diabetic patients as compared to control subjects of both genders (p < 0.001). The urinary levels of these elements were found to be higher in the diabetic patients than in the age-matched healthy controls. In contrast, high mean values of Cu and Fe were detected in scalp hair and blood from patients versus the nondiabetic subjects, but the differences found in blood samples was not significant (p < 0.05). These results are consistent with those obtained in other studies, confirming that deficiency and efficiency of some essential trace metals may play a role in the development of diabetes mellitus.
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PMID:Copper, chromium, manganese, iron, nickel, and zinc levels in biological samples of diabetes mellitus patients. 1819 74

Type 1 diabetes (T1D) is characterized by autoimmunity against pancreatic islets, and autoantibodies may be present for years before diagnosis. Environmental factors during early life, including drinking water, may play a role in pathogenesis of T1D. The German BABYDIAB study is a prospective observational study that followed newborn offspring of mothers or fathers with T1D from birth to 17 years of age. The present study was a nested case-control analysis, where subjects with islet autoimmunity were defined as cases (n=95), those without as controls (n=139). Drinking water quality was obtained from the German Water Supply Authorities for the participating families for the first year of the child's life. There was no significant association between water acidity or drinking water quality (concentration of minerals and elements) and islet autoimmunity risk. Increased progression to diabetes in islet autoantibody-positive children was associated with exposure to water with lower pH values (less than cohort median, 7.62; odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.1-5.7; p=0.03) but was not significant after correction for multiple comparisons. Concentrations of nitrate, nitrite, iron, aluminum, and manganese were not associated with risk of T1D progression. This is the first prospective study with water quality measured before the onset of islet autoimmunity and T1D. Consistent with a previous cross-sectional case-control study, we found an association between drinking water pH and the rate of T1D development in at-risk children. The association is marginal and requires validation in other prospective cohorts.
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PMID:Exposure to environmental factors in drinking water: risk of islet autoimmunity and type 1 diabetes--the BABYDIAB study. 1850 Jun 77

Reversible phosphorylation of proteins regulates numerous aspects of cell function, and abnormal phosphorylation is causal in many diseases. Pyruvate dehydrogenase complex (PDC) is central to the regulation of glucose homeostasis. PDC exists in a dynamic equilibrium between de-phospho-(active) and phosphorylated (inactive) forms controlled by pyruvate dehydrogenase phosphatases (PDP1,2) and pyruvate dehydrogenase kinases (PDK1-4). In contrast to the reciprocal regulation of the phospho-/de-phospho cycle of PDC and at the level of expression of the isoforms of PDK and PDP regulated by hormones and diet, there is scant evidence for regulatory factors acting in vivo as reciprocal "on-off" switches. Here we show that the putative insulin mediator inositol phosphoglycan P-type (IPG-P) has a sigmoidal inhibitory action on PDK in addition to its known linear stimulation of PDP. Thus, at critical levels of IPG-P, this sigmoidal/linear model markedly enhances the switchover from the inactive to the active form of PDC, a "push-pull" system that, combined with the developmental and hormonal control of IPG-P, indicates their powerful regulatory function. The release of IPGs from cell membranes by insulin is significant in relation to diabetes. The chelation of IPGs with Mn2+ and Zn2+ suggests a role as "catalytic chelators" coordinating the traffic of metal ions in cells. Synthetic inositol hexosamine analogues are shown here to have a similar linear/sigmoidal reciprocal action on PDC exerting push-pull effects, suggesting their potential for treatment of metabolic disorders, including diabetes.
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PMID:Reciprocal control of pyruvate dehydrogenase kinase and phosphatase by inositol phosphoglycans. Dynamic state set by "push-pull" system. 1876 79

The metabolic syndrome (MS) has become a worldwide health problem. It is difficult for patients to follow a diet/exercise regime that would improve their symptoms, therefore the investigation of agents that may deal with its more serious aspects is an important medical field for research. The cardiovascular consequences associated with the syndrome and some of the therapeutic approaches are discussed. The different agents can be divided into several groups: Inorganic/ organic: Zinc complexes with garlic components as insulino-mimetics; Selenium as antioxidant; Copper, Zinc and Manganese as microcomponents of antioxidant enzymes. Organic: Natural or Synthetic: Glycine is effective in lowering blood pressure, TBARS, intra-abdominal fat tissue and triglycerides in sucrose-fed rats. Pharmaceutical products: Fibrates, Lipid-lowering drugs. Antidiabetics. Anti-gout agents. On the other hand there are natural products such as those of animal origin: Sex hormones (also synthetic) used in the problems of menopause and hypoandrogenism frequently found in the MS, antioxidant Omega-3-oils (fish oils) or Vegetal: for example Digitalis pupurea, century-old cardiovascular medication as well as Magnolia officinalis; Spirulina maxima with beneficial effects as antioxidant and lipid-lowering agent, among others. Prickly Pear Cacti. (Opuntia Ficus- Indica Cochlospermum vitifolium (Willd.) Spreng) whose many properties against diabetes and hypercholesterolemia have been empirically known for many years. Perezone (from Perezia plants, a.k.a. Peonia) described as an antiplatelet aggregating agent. The mixed elements in the Mediterranean diet: Fish, salads (peppers, tomatoes), olive oil, garlic, red wine which combines fish oils, garlic and avocado as well as antioxidants from the rest of its components.
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PMID:Medicinal agents in the metabolic syndrome. 1885 36

Loss of beta-cell function in type 1 and type 2 diabetes leads to metabolic dysregulation and inability to maintain normoglycemia. Noninvasive imaging of beta-cell function in vivo would therefore provide a valuable diagnostic and research tool for quantifying progression to diabetes and response to therapeutic intervention. Because manganese (Mn(2+)) is a longitudinal relaxation time (T1)-shortening magnetic resonance imaging (MRI) contrast agent that enters cells such as pancreatic beta-cells through voltage-gated calcium channels, we hypothesized that Mn(2+)-enhanced MRI of the pancreas after glucose infusion would allow for noninvasive detection of beta-cell function in vivo. To test this hypothesis, we administered glucose and saline challenges intravenously to normal mice and mice given high or low doses of streptozotocin (STZ) to induce diabetes. Serial inversion recovery MRI was subsequently performed after Mn(2+) injection to probe Mn(2+) accumulation in the pancreas. Time-intensity curves of the pancreas (normalized to the liver) fit to a sigmoid function showed a 51% increase in signal plateau height after glucose stimulation relative to saline (P < 0.01) in normal mice. In diabetic mice given a high dose of STZ, only a 9% increase in plateau signal intensity was observed after glucose challenge (P = not significant); in mice given a low dose of STZ, a 20% increase in plateau signal intensity was seen after glucose challenge (P = 0.02). Consistent with these imaging findings, the pancreatic insulin content of high- and low-dose STZ diabetic mice was reduced about 20-fold and 10-fold, respectively, compared with normal mice. We conclude that Mn(2+)-enhanced MRI demonstrates excellent potential as a means for noninvasively monitoring beta-cell function in vivo and may have the sensitivity to detect progressive decreases in function that occur in the diabetic disease process.
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PMID:Noninvasive assessment of pancreatic beta-cell function in vivo with manganese-enhanced magnetic resonance imaging. 1911 76

Evidence suggests an association between obesity and oxidative stress caused by superoxide production. Since the dismutation of superoxide is catalyzed by superoxide dismutase enzymes, we tested the association between obesity and Ala16Val manganese-dependent superoxide dismutase gene (MnSOD) polymorphism. We analyzed 815 free-living community subjects (> or =60 years old) grouped into subjects who were either obese (BMI > or = 30 kg/m(2)) or non-obese (BMI < 25 kg/m(2)). Additionally, we investigated the possible interaction between the Ala16Val MnSOD gene polymorphism and obesity in the modulation of biochemical and nutritional variables. We found a positive association between MnSOD polymorphism and obesity, since higher VV frequency (28.2%) was observed in the obese group (P = 0.002, odds ratio 1.949, 95% CI: 1.223-3.008). This result was independent of sex, age, diabetes, dyslipidemia, hypertension, and metabolic syndrome. A possible biological explanation of the association described here could be a chronic state of superoxide enzyme imbalance present in VV carriers, which could affect differential metabolic pathways contributing to the obese state.
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PMID:Association between manganese superoxide dismutase (MnSOD) gene polymorphism and elderly obesity. 1926 96

The present study was conducted to investigate the effects of chromium histidinate (CrHis) against experimentally induced type II diabetes and on chromium (Cr), zinc (Zn), selenium (Se), manganese (Mn), iron (Fe), and copper (Cu) in serum, liver, and kidney of diabetic rats. The male Wistar rats (n = 60, 8 weeks old) were divided into four groups. Group I received a standard diet (12% of calories as fat); group II were fed standard diet and received CrHis (110 mcg CrHis/kg body weight per day); group III received a high-fat diet (HFD; 40% of calories as fat) for 2 weeks and then were injected with streptozotocin (STZ) on day 14 (STZ, 40 mg/kg i.p.; HFD/STZ); group IV were treated as group III (HFD/STZ) but supplemented with 110 mcg CrHis/kg body weight per day. The mineral concentrations in the serum and tissue were determined by atomic absorption spectrometry. Compared to the HFD/STZ group, CrHis significantly increased body weight and reduced blood glucose in diabetic rats (p < 0.001). Concentrations of Cr, Zn, Se, and Mn in serum, liver, and kidney of the diabetic rats were significantly lower than in the control rats (p < 0.0001). In contrast, higher Fe and Cu levels were found in serum and tissues from diabetic versus the non-diabetic rats (p < 0.001). Chromium histidinate supplementation increased serum, liver, and kidney concentrations of Cr and Zn both in diabetic and non-diabetic rats (p < 0.001). Chromium supplementation increased Mn and Se levels in diabetic rats (p < 0.001); however, it decreased Cu levels in STZ-treated group (p < 0.001). Chromium histidinate supplementation did not affect Fe levels in both groups (p > 0.05). The results of the present study conclude that supplementing Cr to the diet of diabetic rats influences serum and tissue Cr, Zn, Se, Mn, and Cu concentrations.
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PMID:The effects of chromium histidinate on mineral status of serum and tissue in fat-fed and streptozotocin-treated type II diabetic rats. 1927 Nov 60

Recently, kidney fibrosis following transplantation has become recognized as a main contributor of chronic allograft nephropathy. In transplantation, transient ischemia is an inescapable event. Reactive oxygen species (ROS) play a critical role in ischemia and reperfusion (I/R)-induced acute kidney injury, as well as progression of fibrosis in various diseases such as hypertension, diabetes, and ureteral obstruction. However, a role of ROS/oxidative stress in chronic kidney fibrosis following I/R injury remains to be defined. In this study, we investigated the involvement of ROS/oxidative stress in kidney fibrosis following kidney I/R in mice. Mice were subjected to 30 min of bilateral kidney ischemia followed by reperfusion on day 0 and then administered with either manganese (III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP, 5 mg/kg body wt ip), a cell permeable superoxide dismutase (SOD) mimetic, or 0.9% saline (vehicle) beginning at 48 h after I/R for 14 days. I/R significantly increased interstitial extension, collagen deposition, apoptosis of tubular epithelial cells, nitrotyrosine expression, hydrogen peroxide production, and lipid peroxidation and decreased copper-zinc SOD, manganese SOD, and glucose 6-phosphate dehydrogenase activities in the kidneys 16 days after the procedure. MnTMPyP administration minimized these postischemic changes. In addition, MnTMPyP administration significantly attenuated the increases of alpha-smooth muscle actin, PCNA, S100A4, CD68, and heat shock protein 47 expression following I/R. We concluded that kidney fibrosis develops chronically following I/R injury, and this process is associated with the increase of ROS/oxidative stress.
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PMID:Reactive oxygen species/oxidative stress contributes to progression of kidney fibrosis following transient ischemic injury in mice. 1945 20


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