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)

We have used the myocarditic coxsackievirus B3 (CB3) infection in Balb/c mice to investigate immunotoxic effects of a ten-week low-dose (0.002 M) administration of nickel chloride (NiCl2) prior to infection. This dose did not influence CB3-induced mortality. Whole-body autoradiography of [63Ni] during the disease showed the pancreas, lungs and myocardium to be new target organs in this disease. Seven days after the inoculation, impulse counting of these organs showed the infection-induced increase of [63Ni] to be 5-fold (P < 0.01) in the pancreas, 2.2-fold (P < 0.05) in the lungs and 1.3-fold (P < 0.05) in the heart. Nickel tended to increase spleen B- and T-cell activities, but thymocyte activity was unaffected. The activity of spleen natural killer (NK) cells decreased by 30% (P < 0.05), whereas blood-cell activity in fact increased by 51% (P < 0.05). The inflammatory and necrotic lesions in the ventricular myocardium seven days after the inoculation covered 3.31% of the tissue section area in infected control mice. This damage was increased by 43% (to 4.74% of the tissue section area) in nickel-treated mice. The response pattern of lymphocyte subsets in situ in myocardial inflammatory lesions was elucidated by an immune histochemical staining technique. The number of cytotoxic T-cells, helper T-cells and Mac 2+ cells (macrophages) in these lesions decreased by 46% (P < 0.05), 41% (P < 0.05) and 27% (not significant), respectively, with the nickel treatment. The number of helper T-cells was negatively correlated to the size of the inflammatory area (r = -0.529, P < 0.02). The results indicate that nickel may contribute to the progression of target organ pathology in infection-induced diseases of an autoimmune and/or inflammatory character, such as diabetes and myocarditis.
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PMID:Changed distribution and immune effects of nickel augment viral-induced inflammatory heart lesions in mice. 805 43

A novel prokaryotic expression vector pGEX-6T was designed for high-level expression of recombinant fusion protein with a histidine-hexapeptide and glutathione-S-transferase at its N-terminus and the recombinant human preproinsulin at its C-terminus. Efficiency of expression was investigated in the Escherichia coli strain CAG456. The synthesized protein was sequestered in an insoluble form in inclusion bodies and was purified to homogeneity by one-step affinity chromatography based on the specific complex formation of the histidine-hexapeptide and a chelating matrix which was charged with Ni2+ ions. The antigenic nature of the purified recombinant preproinsulin fusion protein was evaluated by ELISA screening for insulin autoantibodies in selected sera from patients with recent-onset type 1 (insulin-dependent) diabetes mellitus classified by the existence of additional autoantibodies reactive against glutamic acid decarboxylase. 14% of the tested sera (n = 43) contained insulin autoantibodies which strongly recognized the recombinant human preproinsulin. Comparable measurements with both recombinant human preproinsulin and mature insulin suggested that the observed autoantigenicity of preproinsulin was mediated by the C-peptide or/and signal peptide.
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PMID:Recombinant human preproinsulin. Expression, purification and reaction with insulin autoantibodies in sera from patients with insulin-dependent diabetes mellitus. 837 Sep 28

A macroscopic low-voltage-activated (LVA) inward current was found in pancreatic beta-cells isolated from NOD mice. However, this current was not present in nondiabetic prone mouse (e.g., Swiss-Webster) pancreatic beta-cells. We performed pharmacological analyses on this current in NOD insulinoma tumor cells (NIT-1). This cell line was developed from pancreatic beta-cells of a transgenic NOD mouse. The sodium-channel blocker, tetrodotoxin (TTX; 2 micromol/l) had no effect on this LVA current. The amplitudes of currents elicited by a -20 mV test pulse retained similarity when the extracellular sodium concentration was increased from 0 to 115 mmol/l; when the extracellular calcium concentration was decreased from 10 to 2 mmol/l, there was an approximate 50% reduction of this current elicited by a -30 mV test pulse. Neither the L-type calcium-channel blocker, nifedipine (3 micromol/l), nor the N-type calcium-channel blocker, omega-CgTx-GVIA (1 micromol/l), at -30 mV produced an appreciable effect. The T-type calcium-channel blockers, nickel (3 micromol/l) and amiloride (250 micromol/l), effectively reduced the peak of this current. In 2 mmol/l calcium external solution, the threshold of voltage-dependent activation of this calcium current was approximately -65 mV, and the peak current occurred at -20 mV. Half-maximum steady-state inactivation was around -43 mV. The mean time constant of slow deactivating tail currents generated by a preceding 20 mV pulse was 2.53 ms. The intracellular free calcium concentration was two- to threefold higher in NOD mouse pancreatic beta-cells compared with Swiss-Webster pancreatic beta-cells. We concluded that there are LVA calcium channels abnormally expressed in NOD mouse beta-cells. This LVA calcium channel may be factorial to the high cytosolic free calcium concentration observed in these cells, and thereby may contribute to the pathogenesis of NOD mouse beta-cells.
Diabetes 1996 Dec
PMID:Abnormally expressed low-voltage-activated calcium channels in beta-cells from NOD mice and a related clonal cell line. 892 51

One hundred and one patients with histologically confirmed prostate cancer and 202 hospital controls individually matched by age (+/- 2 years), hospital admittance and place of residence, were interviewed during the period 1990-94 in two towns in central Serbia (Yugoslavia). In an analysis using multivariate logistic regression, the followng factors were significantly related to prostate cancer: (1) occupational physical activity during the year preceding the disease [odds ratio (OR)=3.87, 95% confidence interval (95% CI)=2.09-7.16]; (2) occupational exposure to asbestos, steel, dyes and lacquers, bitumen, pitch, iron, nickel, lead, fertilizer and certain other agents (OR=2.13, 95% CI=1.05-4.32); (3) nephrolithiasis (OR=4.52, 95% CI=1.34-15.30); (4) 'other' diseases in medical history such as chronic bronchitis, chronic rheumatic diseases, hypertension, cardiomyopathy, diabetes mellitus, renal diseases, eye diseases and tuberculosis (OR=3.14, 95% CI=1.56-6.33); (5) a greater number (> or = 3) of brothers (OR=2.08, 95% CI=1.35-3.22); and (6) greater numbers (> or = 8) of sexual partners (OR=2.24, 95% CI=1.13-4.44). Marital status, age at first marriage, educational level, age at first sexual intercourse, frequency of sexual intercourse, venereal diseases, tonsillectomy, appendectomy, hernia inguinale and hydrocele, anthropometric characteristics, smoking history, sport and recreational activities and family history of prostatic neoplasms were not found to be independently related to prostate cancer.
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PMID:Case-control study of risk factors for prostate cancer. 893 56

We report a new effective system for expression of FLAG and six histidine tagged TSH receptor in mammalian cells using recombinant vaccinia virus. HeLa cells infected with recombinant virus produced large amounts of human TSH receptor of approximately 150,000 functional molecules per cell. This value is one to two orders of magnitude higher than those in thyroid cells and is comparable with receptor number of the best stably transfected mammalian cell clones previously described. Vaccinia virus produced TSH receptor was able to bind TSH (Kd of 2.1 +/- 0.1 x 10(-10) M) and Graves'disease autoantibodies. TSH caused an increase of the intracellular cAMP level in infected HeLa cells in a concentration-dependent manner, demonstrating the coupling of expressed recombinant TSH receptor to the cAMP second messenger system of the cells. 6His-tagged recombinant TSH receptor was immobilized on Ni2+ nitrilotriacetic acid-agarose. Bound receptor was fully functional, interacting with both TSH and Graves' disease autoantibodies in patient sera. The solid phase bound TSH receptor technique provides a new and simple method for the diagnosis of autoimmune diseases.
Exp Clin Endocrinol Diabetes 1997
PMID:Expression of a functional tagged human thyrotropin receptor in HeLa cells using recombinant vaccinia virus. 935 57

We have previously found that spinal dorsal horn neurons from streptozotocin-diabetic rats, an animal model for diabetes mellitus, show the prominent changes in the mechanisms responsible for [Ca2+]i regulation. The present study aimed to further characterize the effects of streptozotocin-induced diabetes on neuronal calcium homeostasis. The cytoplasmic Ca2+ concentration ([Ca2+]i) was measured in Fura-2AM-loaded dorsal horn neurons from acutely isolated spinal cord slices using fluorescence technique. We studied Ca2+ entry through plasmalemmal Ca2+ channels during potassium (50 mM KCl)-induced depolarization. The K+-induced [Ca2+]i elevation was inhibited to a different extent by nickel ions, nifedipine and omega-conotoxin suggesting the co-expression of different subtypes of plasmalemmal voltage-gated Ca2+ channels. The suppression of [Ca2+]i transients by Ni2+ (50 microM) was the same in control and diabetic neurons. On the other hand, inhibition of [Ca2+]i transients by nifedipine (50 microM) and omega-conotoxin (1 microM) was much greater in diabetic neurons compared with normal animals. These data suggest that under diabetic conditions the activity of N- and L- but not T-type voltage-gated Ca2+ channels substantially increased in dorsal horn neurons.
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PMID:Effect of streptozotocin-induced diabetes on the activity of calcium channels in rat dorsal horn neurons. 1065 32

Although nickel is the metal most commonly implicated in systemic contact dermatitis, other metals such as chromate have also been known to cause dermatitis when ingested. Chromium picolinate has been espoused as a nutritional supplement. Allegedly, it helps control blood sugar in diabetes and may reduce cholesterol and blood pressure levels.
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PMID:Systemic contact dermatitis caused by oral chromium picolinate. 1069 66

Nitric oxide is an important bioactive signaling molecule that mediates a variety of normal physiological functions which, if altered, could contribute to the genesis of many pathological conditions, including diabetes. In the present study we have shown the involvement of NO in nickel-induced hyperglycemia in male albino rats. Administration of nickel chloride (25 to 100 micromol/kg; ip) to overnight-fasted rats resulted in significant dose and time-dependent increase in plasma glucose, attaining maximum level at 1 h posttreatment and thereafter decreasing to normal levels by 4 h. The involvement of NO in nickel-induced hyperglycemia was evident by the observation that pretreatment of rats with NG-monomethyl-l-arginine (10 to 50 micromol/kg; ip), an inhibitor of nitric oxide synthase (NOS), significantly attenuated the nickel-mediated increase in the plasma glucose levels in a dose-dependent fashion. The activity of Ca(2+)-dependent NOS (constitutive form, c-NOS) was found to be significantly elevated in adrenals (5.5-fold) and brain (1.4-fold) at 1 and 2 h posttreatment, attaining normal levels by 4 h. In contrast, the activity of c-NOS in pancreas was significantly decreased (2.8-fold) with a concomitant increase (11.6-fold) in inducible NOS (i-NOS) at the same time interval. As observed by immunoblot analysis, a significant increase in i-NOS protein expression in the pancreas was observed at 1 and 2 h posttreatment. This was associated with a significant elevation in cGMP levels in adrenals, brain, and pancreas, possibly via the stimulation of cytosolic guanylate cyclase. This elevation in cGMP was abolished by low concentration of hemoglobin. These effects were associated with the accumulation of nickel in the target tissues. Taken together, our data suggest that nickel causes a significant increase in the levels of (i) cGMP and c-NOS in adrenals and brain and (ii) i-NOS in pancreas. These events may be responsible for modulating the release of insulin from pancreas finally leading to hyperglycemic condition in rats.
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PMID:Involvement of nitric oxide in nickel-induced hyperglycemia in rats. 1083 93

Activity of reactive oxygen species is elevated in diabetes mellitus and has been implicated in the destruction of cellular components. The toxic effect of reactive oxygen species was investigated by testing the effect of H2O2 on [Ca2+]i in isolated islets of Langehans. H2O2 increased [Ca2+]i in a dose-dependent manner, which was irreversible at high concentrations. The maximum effect of H2O2 on [Ca2+]i was larger than those of KCl, glucose, ATP, carbachol and endothelin-1. The effect of H2O2 was only partially attenuated by removal of external Ca2+ and by the in-organic Ca2+ channel blocker nickel, but was not blocked by voltage-dependent or -independent Ca2+ channel blockers nimodipine, nicardipine, SK&F 96365, econazole and lanthanum. H2O2, disrupted [Ca2+]i homeostasis in islets by affecting both release and influx of Ca2+ and causing dysfunction of Ca2+ clearance systems and may contribute to the pathological process of diabetes.
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PMID:Mechanisms of [Ca2+]i elevation by H2O2 in islets of rats. 1120 96

The 9 kinds of Chinese traditional medicines which are used to cure diabetes including Xiaokewan, Yuquanwan, Kelening, Jiangtangshu, Jiangtang I-V are digested with HNO3-HClO4 (4:1) mixed acid. The 12 trace elements of copper, zinc, nickel, cobalt, manganese, chromium, molybdenum, iron, calcium, magnesium, cadmium and lead in the solution are determined by atomic absorption spectrometry. Its recovery ratio by standard addition is 97%-105%, and RSD is lower than 5%. This method has good accurate. The results obtained show that except Cd and Pb all other ten trace elements contents in the drug are high. The results of this paper provide useful data for studying the relation between the contents of these trace elements and the medical effect.
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PMID:[Determination of trace elements in Chinese traditional medicines by atomic absorption spectrometry]. 1293 50


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