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)

When either rat or human erythrocytes were incubated for 90-180 min in bicarbonate-buffered media prepared in 2H2O rather than 1H2O, the generation of 3HOH from D-[5-3H]glucose, the production of either 14CO2 or 14C-labelled acidic metabolites from D-[U-14C]glucose and the production of L-lactic acid from unlabelled D-glucose were decreased, to a variable extent but, in no case, by more than 30%. Hence, total substitution of 1H2O by 2H2O provides a suitable tool to study by NMR the generation of 2H-enriched L-lactic acid generated from exogenous D-[1-13C]glucose or D-[6-13C]glucose and, hence, to further explore the diabetes-induced alteration of hydrogen isotopes intermolecular transfer in the reaction catalyzed by phosphoglucoisomerase.
Diabetes Res 1992 Jan
PMID:Effect of 2H2O upon D-glucose metabolism in rat and human erythrocytes. 133 14

Localized 1H NMR spectra of human brain in vivo are affected by signal overlap, strong spin-spin coupling, and complex J modulation, and therefore differ considerably from those obtained at higher magnetic fields. This paper deals with the assignment of 1H NMR resonances of cerebral metabolites under the experimental conditions used for human investigations. Conventional 7.0-T FID spectra and 2.0 T localized, short echo time STEAM spectra (TE = 20 ms) of aqueous metabolite solutions are compared to in vivo brain spectra of human volunteers and patients. In addition to singlet resonances from N-acetyl aspartate (NAA), creatines, and cholines, short echo time STEAM spectra exhibit multiplets due to the NAA aspartyl group, glutamate, taurine, and myo-inositol. Enhanced levels of cerebral glutamine are detected in patients with liver cirrhosis. For the first time elevated levels of brain glucose are observed in patients with diabetes mellitus.
NMR Biomed 1991 Apr
PMID:On the identification of cerebral metabolites in localized 1H NMR spectra of human brain in vivo. 167 88

With radiotracer and 13C nuclear magnetic resonance (13C-NMR) methods, we studied the time course of glycogen resynthesis after three 90-s episodes of hypoxemia in both control and diabetic rats in vivo. Glycogen synthesis was measured in the presence and absence of infused insulin and compared with the changes in glycogen synthase (GS) and phosphorylase activities. We observed in 13C-NMR spectra the expected mobilization of glycogen during hypoxia in vivo. In control rats with or without exogenous insulin, this was followed by a rapid resynthesis of glycogen during a 40-min recovery period. A marked activation of GS was observed by 10 min (glucose-6-phosphate-independent form of GS [GSl] = 0.65 mumol.min-1.g-1 or 92% of total GS), and activation persisted up to 40 min in both groups. Glycogen synthesis during the recovery period averaged 0.51 and 0.45 mumol.min-1.g-1 in the saline- and insulin-treated rats, respectively. In the diabetic rats by 10 min after hypoxemia, GSl increased only modestly in both saline-treated (0.16 mumol.min-1.g-1) and insulin-treated (0.21 mumol.min-1.g-1) rats, and activation persisted up to 40 min only with insulin treatment. Glycogen synthesis was slower in the diabetic rats given insulin (0.28 mumol.min-1.g-1) and essentially absent in the saline-treated rats (0.03 mumol.min-1.g-1) compared with controls. We conclude that recovery from hypoxemia is accompanied by a marked activation of GSl and rapid rates of glycogen synthesis in nondiabetic rats, and diabetes markedly blunts this response. Acute insulin infusion only partially overcomes this block.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Mar
PMID:Hypoxemic stimulation of heart glycogen synthase and synthesis. Effects of insulin and diabetes mellitus. 190 Feb 48

Crystal structures of insulin have been determined in various distinct forms, the relevance of which to receptor recognition has long been the subject of speculation. Recently the crystal structure of an inactive insulin analogue has been determined and, surprisingly, found to have a conformation identical to native insulin. On this basis Dodson and colleagues have suggested that the known insulin crystal structures reflect an inactive conformation, and that a change in conformation is required for activity--specifically, the carboxy terminal residues of the B-chain are proposed to separate from the amino terminal residues of the A-chain. Here we report the solution structure of an active insulin mutant, determined by two-dimensional NMR, which supports this hypothesis. In the mutant, the carboxy terminal beta-turn and beta-strand of the B-chain are destabilized and do not pack across the rest of the molecule. We suggest that analogous detachment of the carboxy terminal region of the B-chain occurs in native insulin on binding to its receptor. Our finding that partial unfolding of the B-chain exposes an alternative protein surface rationalizes the receptor-binding properties of a series of anomalous insulin analogues, including a mutant insulin associated with diabetes mellitus in man.
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PMID:Receptor binding redefined by a structural switch in a mutant human insulin. 196 Dec 50

1H-NMR spectra of 60 human urine specimens were recorded without pretreatment by a JEOL FX 90 Q spectrometer operating at 89.55 MHz. The signals of the methyl protons of creatinine (3.04 +/- 0.02 ppm) were observed in all spot fasting morning urine samples collected from 7 healthy persons, 10 patients with nephrotic syndrome and 43 patients with diabetes mellitus. The concentrations of creatinine measured by NMR spectroscopy (Y) and the chemical assay based on the Jaffe reaction (X), over the range of 19-190 mg/dl, were compared by the least-squares linear regression analysis (Y = 6.7799 + 0.6717 X). The mean urinary creatinine concentration by NMR spectroscopy appeared to be lower than that obtained by the Jaffe reaction at the normal and high normal levels. In the urine of 20 diabetic patients with an average blood glucose of 251.30 +/- 50.26 (SD) mg/dl typical spectra of the multiple large signals of glucose protons at position from 3.13 +/- 0.04 to 4.04 +/- 0.12 (SD) ppm were shown. Moreover, some urinary metabolites and amino acids spectra were occasionally detected at one time.
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PMID:Identification of urinary metabolites and quantitative measurement of creatinine by a proton nuclear magnetic resonance spectrometry. 226 55

Phosphorylcholine (P-choline) is a precursor of the phospholipids in the lens membrane. A human lens normally contains approx. 1 mM P-choline but this is significantly lowered in some cataractous lenses. A normal rat lens contains a very high concentration (11 mM). We found that rat lens P-choline was depleted drastically when the lenses were exposed to hyperglycemic conditions either in culture, with galactose or xylose, or in vivo by streptozotocin-induced diabetes. The lens P-choline level was measured by fractionating the organic phosphates in the lens homogenate using an ion exchange column, or by quantitating the P-choline 31P NMR intensity in intact lenses. The results of both the chemical method and the noninvasive method agreed remarkably well. Besides the change in P-choline, the choline influx was also drastically reduced both in lenses from diabetic rats and in lenses incubated with 30 mM xylose. In addition, the ATP concentration was greatly diminished under similar conditions. The changes in P-choline, choline, and ATP could all be prevented in the presence of an aldose reductase inhibitor (ARI). It is thus concluded that these changes in phospholipid precursors may result from lenticular membrane defects caused by hyperglycemic stress. The effect of the lowered precursors on lipid biosynthesis was observed, and surprisingly showed a more rapid phospholipid-biosynthesis in the 2-week diabetic rat lens than in the 3-day diabetic rat lens.
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PMID:The effect of an aldose reductase inhibitor on lens phosphorylcholine under hyperglycemic conditions: biochemical and NMR studies. 249 85

In vivo deuterium magnetic resonance spectroscopy was used to measure fat utilization rates in diabetic and non-diabetic obese and non-obese mice. Monosodium glutamate-treated mice were used as a model for obesity, and diabetes was induced by administration of streptozotocin. Deuterium levels were enhanced by addition of D2O to drinking water (10% v/v) for a period of 14 days. The deuterium magnetic resonance signals of the body water and adipose tissue were then monitored to measure the rate of deuterium loss from the body. The rates of fat utilization for obese mice were significantly lower (75%, p less than 0.05) (halflife, t1/2 = 113 +/- 13 days) than the rates for non-obese mice (t1/2 = 30.0 +/- 9.0 days). The induction of diabetes caused a large (90%) but proportionally similar increase in fat utilization for both groups of mice (obese, t1/2 = 11.0 +/- 5.2; non-obese, t1/2 = 3.0 +/- 0.9). The results suggest that the induction of diabetes in obese mice does not affect the utilization of fat as a metabolic fuel. These preliminary studies indicate that deuterium magnetic resonance spectroscopy may be a useful technique for non-invasive determination of the rates of fat utilization in vivo.
NMR Biomed 1989 Jul
PMID:The use of in vivo 2H NMR spectroscopy to investigate the effects of obesity and diabetes mellitus upon lipid metabolism in mice. 253 3

31P NMR was used to study the erythrocytes of three patients who exhibited a familial multisystem disease characterized by fatty liver, diabetes and nonspherocytic hemolytic anemia of unknown etiology. 31P NMR measurements disclosed an abnormally high level of intracellular inorganic phosphate (Pi) and an abnormally low level of ATP in the erythrocytes 6 h after blood withdrawal from proband (I-1). This finding suggested that ATP was markedly decreased in the red cells of this proband, as compared with those of normal subjects. Time-dependent changes of 31P NMR spectra of the erythrocytes from the two daughters (II-1, II-2) of the proband demonstrated clearly an enhanced decomposition of ATP with a concomitant increment of Pi. Several ATP-consuming enzymes in erythrocytes, such as those in the Embden-Meyerhof system, pentose phosphate pathway enzymes, Na+, K(+)-ATPase and Ca2+, Mg2(+)-ATPase, were within normal limits of activity, but Mg2(+)-ATPase was drastically above the normal limit. The Mg2(+)-ATPase activity was 3 times higher in the red cell membranes of these patients than in those from normal subjects.
NMR Biomed 1989 Sep
PMID:An interesting syndrome of hemolytic anemia, degeneration of the liver and diabetes associated with a high red cell Mg-ATPase, detected by 31P NMR spectroscopy. 253 4

Proper determination of vascular haemodynamics requires measurement of flow and pressure. The objective of this study is to provide methods of measurement of the arterial flow, which may currently be performed via an external approach. The techniques in question include non-invasive electromagnetic flowmetry (NMF) and flowmetry by NMR. NMF uses external magnets, the signal is collected by common cutaneous electrodes; the equipment is simple and may be used in a cardio-angeiology office. It main advantage lies in the screening of arterial diseases (very reproductable and sensitive), monitoring of the treatment (unrelated to the operator), study of hardened arteries (diabetes). Flowmetry by NMR requires a more sophisticated and costly equipment; it permits staged measurements, as well as a scan permitting measurements in one single artery; it is mostly used in specialized centres. Arterial lesions may be defined as not yet significant when only the blood pressure is considered, while the pulsatile flow is already altered; transluminal angioplasties performed in these circumstances, permit to restore the clinical picture as well as increasing twofold the initial flow.
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PMID:[The necessary advantage of measuring the pulsatile arterial flow of the limbs in patients with arterial disease]. 259 16

The aromatic 1H NMR resonances of the insulin monomer are assigned at 500 MHz by comparative studies of chemically modified and genetically altered variants, including a mutant insulin (PheB25----Leu) associated with diabetes mellitus. The two histidines, three phenylalanines, and four tyrosines are observed to be in distinct local environments; their assignment provides sensitive markers for studies of tertiary structure, protein dynamics, and protein folding. The environments of the tyrosine residues have also been investigated by photochemically induced dynamic nuclear polarization (photo-CIDNP) and analyzed in relation to packing constraints in the crystal structures of insulin. Dimerization involving specific B-chain interactions is observed with increasing protein concentration and is shown to depend on temperature, pH, and solvent composition. In the monomer large variations are observed in the line widths of amide resonances, suggesting intermediate exchange among conformational substates; such substates may relate to conformational changes observed in different crystal states and proposed to occur in the hormone-receptor complex. Additional evidence for multiple conformations in solution is provided by comparative studies of an insulin analogue containing a peptide bond between residues B29 and A1 (mini-proinsulin). This analogue forms dimers and higher-order oligomers under conditions in which native insulin is monomeric, suggesting that the B29-A1 peptide bond stabilizes a conformational substate favorable for dimerization. Such stabilization is not observed in corresponding studies of native proinsulin, in which a 35-residue connecting peptide joins residues B30 and A1; this extended tether is presumably too flexible to constrain the conformation of the B-chain. The differences between proinsulin and mini-proinsulin suggest a structural mechanism for the observation that the fully reduced B29-A1 analogue folds more efficiently than proinsulin to form the correct pattern of disulfide bonds. These results are discussed in relation to molecular mechanics calculations of insulin based on the available crystal structures.
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PMID:Two-dimensional NMR and photo-CIDNP studies of the insulin monomer: assignment of aromatic resonances with application to protein folding, structure, and dynamics. 269 17


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