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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of insulin in vitro on perfused liver from streptozotocin-diabetic rats and their untreated littermates during gluconeogenesis from either [3-13C]alanine + ethanol or [2-13C]pyruvate + NH4Cl + ethanol were studied by 13C NMR. A 13C NMR determination of the rate of pyruvate kinase flux under steady-state conditions of active gluconeogenesis was developed; this assay includes a check on the reuse of recycled pyruvate. The preparations studied provided gradations of pyruvate kinase flux within the confines of the assay's requirement of active gluconeogenesis. By this determination, the rate of pyruvate kinase flux was 0.74 +/- 0.04 of the gluconeogenic rate in liver from 24-h-fasted controls; in liver from 12-h-fasted controls, relative pyruvate kinase flux increased to 1.0 +/- 0.2. In diabetic liver, this flux was undetectable by our NMR method. Insulin's hepatic influence in vitro was greatest in the streptozotocin model of type 1 diabetes: upon treatment of diabetic liver with 7 nM insulin in vitro, a partial reversal of many of the differences noted between diabetic and control liver was demonstrated by 13C NMR. A major effect of insulin in vitro upon diabetic liver was the induction of a large increase in the rate of pyruvate kinase flux, bringing relative and absolute fluxes up to the levels measured in 24-h-fasted controls. By way of comparison, the effects of ischemia on diabetic liver were studied by 13C NMR to test whether changes in allosteric effectors under these conditions could also increase pyruvate kinase flux. A large increase in this activity was demonstrated in ischemic diabetic liver.
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PMID:Effects of insulin on perfused liver from streptozotocin-diabetic and untreated rats: 13C NMR assay of pyruvate kinase flux. 303 Apr 12

Wolfram's syndrome, also known as DIDMOAD syndrome, includes juvenile diabetes mellitus and optic atrophy variously associated with diabetes insipidus and deafness. We describe the neurological findings in 5 patients with Wolfram's syndrome. All patients had a neurological examination and were subjected electrophysiological and brain imaging including CT scan and, in one patient, MRI. There were two pairs of brothers and a sporadic case with paternal consanguinity suggesting recessive inheritance. Neurological abnormalities were found in four patients including dysarthria, seizures, anosmia, nystagmus, ataxia and changes in the electroencephalograms, electroretinograms and evoked potentials. In contrast with previous reports, four patients had abnormal brain CT scan with prominent atrophy of the brainstem. In the patient studied with NMR, severe brainstem and cerebellar atrophy was found. These neuroradiological findings are reminiscent of those described in olivopontocerebellar atrophy and are in agreement with previous pathological studies. We conclude that Wolfram's syndrome includes phenotypical manifestations of olivopontocerebellar atrophy. This reinforces the opinion that olivopontocerebellar atrophy is a nonspecific syndrome of varied causes.
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PMID:[Neurologic manifestations in Wolfram's syndrome]. 833 58

Magnesium ions (Mg2+) are pivotal in the transfer, storage and utilization of energy; Mg2+ regulates and catalyzes some 300-odd enzyme systems in mammals. The intracellular level of free Mg2+ ([Mg2+]i) regulates intermediary metabolism, DNA and RNA synthesis and structure, cell growth, reproduction, and membrane structure. Mg2+ has numerous physiological roles among which are control of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, blood pressure and peripheral blood flow. Mg2+ modulates and controls cell Ca2+ entry and Ca2+ release from sarcoplasmic and endoplasmic reticular membranes. Since the turn of this century, there has been a steady and progressive decline of dietary Mg intake to where much of the Western World population is ingesting less than an optimum RDA. Geographic regions low in soil and water Mg demonstrate increased cardiovascular morbidity and mortality. Dietary deficiency of Mg2+ results in loss of cellular K+ and gain of cellular Na+ and calcium ions (Ca2+). Blood normally contains Mg2+ bound to proteins, Mg2+ complexed to small anion ligands and free ionized Mg2+ (IMg2+). Most clinical laboratories only now assess the total Mg, which consists of all three Mg fractions. Estimation of the IMg2+ level in serum or plasma by analysis of ultrafiltrates (complexed Mg + IMg2+) is somewhat unsatisfactory, as the methods employed do not distinguish the truly ionized form from Mg2+ bound to organic and inorganic anions. Because the levels of these ligands can vary significantly in numerous pathological states, it is desirable to directly measure the levels of IMg2+ in complex matrices such as whole blood, plasma and serum. Using novel ion selective electrodes (ISE's), we have found that there is virtually no difference in IMg2+, irrespective of whether one samples whole blood, plasma or serum. These data demonstrate that the mean concentration of IMg2+ in blood is about 600 mumoles/litre (0.54-0.65 mmol/L, 95% Cl); 65-72% of total Mg being free or biologically-active Mg2+. Use of the NOVA and KONE ISE's for IMg2+ on plasma and sera from patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants, liver transplants, during and before cardiac surgery, ischemic heart disease [IHD], headaches, pregnancy, neonatal period, non-insulin dependent diabetes (NIDDM), end-stage renal disease [ESRD], hemodialyse [HEM], and continuous ambulatory peritoneal dialysis (CAPD), hypertension, myocardial infarction [AMI] and after excessive dietary intake of Mg), has revealed interesting data. The results indicate that long-term renal transplant patients, headache, pregnant, NIDDM, ESRD, HEM, CAPD, AMI, hypertensive, and IHD subjects exhibit, on the average significant depression in IMg2+ but not TMg. Use of 31P-NMR spectroscopy on red blood cells, from several of these disease states, to assess free intracellular Mg ([Mg2+]i demonstrates a high correlation (r = 0.5-0.8) between IMg2+ and [Mg2+]i. Increased dietary load of Mg, for only 6 days, in human volunteers, resulted in significant elevations in serum IMg2+ but not TMg. Correlations between the clinical course of several of the above disease syndromes and the fall in IMg2+ and [Mg2+]i were found. The ICa2+/IMg2+ ratio appears, from our data, to be an important guide for signs of peripheral vasoconstriction, ischemia or spasm and possibly atherogenesis. Overall, our data point to important uses for ISE's for IMg2+ in the diagnosis and treatment of disease states.
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PMID:Role of magnesium in patho-physiological processes and the clinical utility of magnesium ion selective electrodes. 886 38

The initial diagnosis and subsequent treatment of rhino-orbital mucormycoses is quite difficult, particularly because the patient may find it difficult to accept aggressive therapeutic protocols, even when free of any endocranial involvement. The authors draw inspiration from a clinical case of rhino-orbital mucormycosis in a patient suffering from decompensated type I diabetes mellitus to discuss the main clinical-diagnostic and therapeutic aspects of this disorder. Timely medical-surgical treatment proves extremely important for prognosis, preventing the intracranial extension of the lesion which is the cause of death in 80% of such cases. As regards the diagnostic protocol, careful clinical, radiological monitoring with CT and NMR--in strict interdisciplinary cooperation between otorhinolaryngologist, radiologist, ophthalmologist, microbiologist and histopathologist--is especially important. Radical surgery, at times demolition, associated with correction of the metabolic decompensation, systemic therapy with Amphotericin B and localbi-weekly medication for three months constitutes the best therapeutic protocol for treatment of this disorder.
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PMID:[Difficulties in the clinical, radiological and therapeutic evaluation of the initial stage of mucormycosis of the rhinosinus]. 1088 55

LDL particle size can be measured by gradient gel electrophoresis (GGE) and NMR. The agreement between the two methods has not been extensively evaluated. Therefore, we measured LDL size by NMR and GGE in 324 individuals (152 with type 1 diabetes and 172 controls). The Spearman correlation between both methods was 0.39 [95% confidence interval (CI) = 0.29, 0.48]. The average difference was 5.38 nm (NMR being smaller), but it increased with increasing LDL size. Less than 50% of people classified as pattern B on GGE were classified as pattern B on NMR (kappa = 0.31; 95% CI = 0.17, 0.45). Agreement was lower for diabetic subjects compared with controls, for women compared with men, and for subjects with triglycerides less than 1.30 mmol/l compared with subjects with triglycerides greater than 1.30 mmol/l. External validation showed that cholesteryl ester transfer rate was related to LDL size on GGE in all subgroups and to LDL size on NMR only in men and nondiabetic subjects. Our findings show that agreement between NMR- and GGE-based LDL size is far from perfect and is not consistent across subgroups of patients. In particular, the two methods should not be assumed to be interchangeable in women and diabetic subjects. Whether NMR or GGE predicts cardiovascular disease risk better has not yet been evaluated.
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PMID:Study of agreement between LDL size as measured by nuclear magnetic resonance and gradient gel electrophoresis. 1499 38

The T-box transcription factor T-bet is known to control lineage commitment and interferon-gamma production by T helper 1 (Th1) CD4 lymphocytes. We report here that T-bet is essential for development of CD8 lymphocyte-dependent autoimmune diabetes (type 1 diabetes [T1D]) in the rat insulin promoter-lymphocytic choriomeningitis virus (LCMV) transgenic model for virally induced T1D. In the absence of T-bet, autoaggressive (anti-LCMV) CD8 lymphocytes were reduced in number and produced less IFN-gamma, but increased IL-2 compared with controls. Further analysis showed that T-bet intrinsically controls the generation, but not apoptosis, maintenance, or secondary expansion of antiviral effector/memory CD8 lymphocytes. This observation points toward a therapeutic opportunity for the treatment of T1D and other autoimmune disorders.
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PMID:T-bet controls autoaggressive CD8 lymphocyte responses in type 1 diabetes. 1509 40

The gene encoding interferon (IFN)-gamma, IFNG, is known as one of the candidate susceptibility genes for type 1 diabetes. In addition, cytokines, including IFN-gamma, play important roles in the pathogenesis of type 1 diabetes. Therefore, we focused on the Th1-specific T-box transcription factor gene (T-bet), which contributes to the induction of the hallmark Th1 cytokine, IFN-gamma. We first screened for polymorphisms in the T-bet gene and detected two microsatellite repeat polymorphisms located in intron 1 and the 3'- flanking region, and two single nucleotide polymorphisms, including a His33Gln substitution within the coding region. By association studies, the Gln-positive phenotype and (CA)14 allele in 3'-flanking region of T-bet were found to be associated with type 1 diabetes in the Japanese population. Furthermore, Gln33 T-bet showed a significantly higher transcriptional activity of the IFNG gene via a dual luciferase reporter assay. Our study suggests the first evidence of an association between type 1 diabetes and polymorphisms in the T-bet gene, and that variation in T-bet transcriptional activity may play a role in the development of type 1 diabetes, possibly through the effect on IFN-gamma production in Th1 cells.
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PMID:Identification of a novel type 1 diabetes susceptibility gene, T-bet. 1524 79

AC137 (pramlintide) is a 37-residue peptide analogue of the hormone amylin. Pramlintide has been studied as an adjunct antihyperglycemic treatment for patients with type 2 or type 1 diabetes who use insulin. This study took an empirical phase diagram (EPD) approach to obtain information about the structural stability of this peptide by compiling thermal perturbation data acquired from multiple spectroscopic methods, including high-resolution second-derivative UV absorbance spectroscopy, optical density, fluorescence, and circular dichroism. This approach enabled us to accomplish two major goals: (1) characterize the structure and physical stability of AC137 and (2) assess the application of EPDs to a small peptide. Results obtained at low concentration of AC137 revealed a peptide with ill-defined structure and insensitivity to pH. Use of isotope exchange NMR confirmed this lack of structure. At the current formulation of pH 4, AC137 exhibited stability at concentrations of 1.8 to 8.8 mg/mL. High concentrations of the peptide showed a tendency to aggregate at pH 6-7.5. Construction of EPDs under the various experimental conditions examined manifested color changes that correlated well with the raw data. The utility and limitations of the EPD approach when applied to weakly structured peptides are discussed.
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PMID:A biophysical characterization of the peptide drug pramlintide (AC137) using empirical phase diagrams. 1787 73

Metabolic profiling of urine presents challenges because of the extensive random variation of metabolite concentrations and the dilution resulting from changes in the overall urine volume. Thus statistical analysis methods play a particularly important role; however, appropriate choices of these methods are not straightforward. Here we investigate constant and variance-stabilization normalization of raw and peak picked spectra, for use with exploratory analysis (principal component analysis) and confirmatory analysis (ordinary and Empirical Bayes t-test) in (1)H NMR-based metabolic profiling of urine. We compare the performance of these methods using urine samples spiked with known metabolites according to a Latin square design. We find that analysis of peak picked and logarithm-transformed spectra is preferred, and that signal processing and statistical analysis steps are interdependent. While variance-stabilizing transformation is preferred in conjunction with principal component analysis, constant normalization is more appropriate for use with a t-test. Empirical Bayes t-test provides more reliable conclusions when the number of samples in each group is relatively small. Performance of these methods is illustrated using a clinical metabolomics experiment on patients with type 1 diabetes to evaluate the effect of insulin deprivation.
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PMID:Interdependence of signal processing and analysis of urine 1H NMR spectra for metabolic profiling. 1995 Sep 23

We have demonstrated previously that BM-derived DCs can prevent diabetes development and halt progression of insulitis in NOD mice, the mouse model of type 1 diabetes. The DC population that was most effective in this therapy had a mature phenotype, expressed high levels of costimulatory molecules, and secreted low levels of IL-12p70. The protective DC therapy induced Treg and Th2 cells in vitro and in vivo. Microarray analysis of therapeutic and nontherapeutic DC populations revealed differences in the expression of OX40L, CD200, Ym-1, CCL2, and CCL5, which could play important roles in the observed DC-mediated therapy. The unique pattern of costimulatory molecules and chemokines expressed by the therapeutic DCs was confirmed by flow cytometry and ELISA. Using a novel cell-labeling and (19)F NMR, we observed that the chemokines secreted by the therapeutic DCs altered the migration of diabetogenic Th1 cells in vivo and attracted Th2 cells. These results suggest that the therapeutic function of DCs is mediated by a combination of costimulatory and chemokine properties that results in the attraction of diabetogenic Th1 and the induction of Th2 and/or Treg differentiation.
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PMID:Gene expression analysis of dendritic cells that prevent diabetes in NOD mice: analysis of chemokines and costimulatory molecules. 2162 31


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