Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemia is often implicated as a cause of acute renal failure. We have investigated the effect of various concentrations of extracellular Mg2+ on the post-ischemic recovery of ATP and low intracellular Na+ in the isolated perfused rat kidney using 31P and triple-quantum filtered (TQ) 23Na-NMR spectroscopy. Following a 1 h period of stopped flow ischemia, the kidneys exposed to 0.3 mM Mg2+ throughout the experiment exhibited a significantly (p < 0.05) decreased post-ischemic fractional recovery of ATP (56 +/- 7%) as well as a significantly (p < 0.05) increased accumulation of P(i) (250 +/- 30%) as compared to kidneys exposed to 1.2 mM Mg2+ throughout (88 +/- 5% recovery of [ATP] and 158 +/- 8% accumulation of [P(i)]). Kidneys exposed to 0.3 mM Mg2+ during the pre-ischemic and ischemic periods but to 1.2 mM Mg2+ during reperfusion also showed better recovery of ATP (83 +/- 6%) and lower accumulation of P(i) (143 +/- 8%) compared to kidneys exposed to low Mg2+ (0.3 mM) throughout the experiment. Measurements of the 23Na TQ signal following ischemia-reperfusion revealed that kidneys exposed to 1.2 mM Mg2+ exhibited significantly improved maintenance of low intracellular Na+ as compared to those exposed to 0.3 mM Mg2+ ([Na+]i = 107 +/- 7% in 1.2 mM Mg2+ vs. 152 +/- 3% in 0.3 mM Mg2+). No significant difference was found in the pre-ischemic basal intracellular free Ca2+ level (as measured by 19F-NMR in combination with 5 FBAPTA) between kidneys perfused with 1.2 mM and 0.3 mM Mg2+, and comparable depletion of ATP occurred during ischemia under both experimental conditions. These data indicate that increased extracellular Mg2+ has a protective effect against post-ischemic damage, probably related to its role in resynthesis of ATP during post-ischemic reperfusion. Our results would imply a greater vulnerability of the kidney to ischemic damage in hypomagnesemic clinical conditions such as alcoholism and diabetes.
 ...
PMID:NMR studies of the effect of Mg2+ on post-ischemic recovery of ATP and intracellular sodium in perfused kidney. 854 43

Diabetic lens glucose metabolism in vivo can be altered by a number of exogenous substrates. We have chosen two, one a glucose epimer (mannose) and the other a glycolytic intermediate (pyruvate), to demonstrate the possibility of this approach. D(+)-Mannose is a D(+)-glucose epimer but in lenses incubated in 35.5 mM mannose, no mannitol (the sorbitol equivalent) was detected, while both lactate production and 31P profile appeared normal. Mannose therefore is a good glucose substitute causing no polyol formation. Mannose metabolism in the rat lens in vivo was then examined. Diabetic rats fed mannose-enriched diet over a period of 14 days showed retardation of changes in 31P metabolites, specifically the levels of phosphorylcholine and glycerophosphorylcholine, suggesting a protective effect. Rat lenses incubated in 35.5 mM glucose in the presence of 5 mM pyruvate (pyr) showed 50% lower sorbitol than without pyr. With 5 mM pyr in the drinking water, i.e. pretreatment in vivo during a 3-day diabetes induction period, the diabetic rat lens accumulated acetate and alanine when incubated in the presence of pyr. The decrease in sorbitol was most likely due to a lower glucose flux rather than an increased polyol dehydrogenase activity. Increasing glucose concentration from 5.5 to 35.5 mM or provision of exogenous pyr both caused an intermediate increase in O2 consumption in the normal lens; a maximal activity was reached with both 35.5 mM glucose and 5 mM pyruvate in the incubating medium. In the diabetic lens, O2 consumption could reach the intermediate but not the maximal level. Dietary pyr pre-treatment also prevented normal and diabetic lenses from maximal pyr-stimulated O2 consumption. The NMR and O2 consumption data together indicated activation of alanine dehydrogenase and saturation of Krebs cycle. It appears that dietary supplement of mannose can preserve 31P membrane metabolites in the diabetic lens. Mannose can be used in conjunction with hypoglycemic therapy for the management of diabetic cataract. In addition, pyruvate may be effective in enhancing lens energy metabolism and lower sorbitol production.
 ...
PMID:Manipulating rat lens glucose metabolism with exogenous substrates. 854 89

A condition similar to insulin-dependent diabetes mellitus (IDDM) was induced in male CD-1 mice by injection of streptozotocin (STZ). Five weeks after treatment, the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus (SOL) muscles were isolated for analysis. Phosphorous metabolites were quantified by 31P-NMR and HPLC, native myosin was characterized electrophoretically, and activities of metabolic enzymes were measured spectrophotometrically. Relative to control animals, STZ-diabetes resulted in a significant 32% decrease in the FM1 isoform of myosin in EDL and a 24% decrease in IM myosin of SOL. Mass-specific activities of phosphofructokinase, citrate synthase, and cytochrome oxidase were significantly lower in SOL from STZ-diabetic mice than in controls by 23, 18, and 36%, respectively. Intracellular ATP was significantly lower in SOL from STZ-diabetic mice than in controls (3.44 +/- 0.20 mumol g-1 wet weight vs. 4.61 +/- 0.20 mumol g-1, respectively), as was creatine phosphate (11.98 +/- 0.80 mumol g-1 wet weight vs. 14.22 +/- 0.44 mumol g-1). In contrast to results from SOL, there were no significant changes in phosphorus metabolites or enzyme activity in EDL. These results show that the effects of IDDM on levels of phosphorus containing metabolites and maximal activities of key regulatory enzymes in muscle are markedly fiber-type specific. It is suggested that the muscle type-specific effects of STZ-diabetes may be a consequence of differential accumulation of intracellular fatty acids.
 ...
PMID:Responses of mouse fast and slow skeletal muscle to streptozotocin diabetes: myosin isoenzymes and phosphorous metabolites. 859 19

Troglitazone (CS-045) is a new oral antidiabetic drug reported to be effective in insulin-resistant diabetes and to show antihypertensive effects. Photooxidation of troglitazone gave the quinone and quinone epoxide as the major final stable products. An intermediate observed by NMR spectroscopy was shown to be the hydroperoxydienone, which is moderately stable at room temperature. The rate constant of singlet oxygen quenching by troglitazone is 2.14 x 10(8) M(-1) s(-1) and the reaction rate constant in acetone-d6 is 8.64 X 10(6) M(-1) s(-1). Only the chroman ring of troglitazone reacts with and quenches singlet oxygen significantly, and its reactivity and products are analogous to those of alpha-tocopherol. The reactivity of CS-45 toward singlet oxygen is much larger than that of the related compounds lacking the chroman ring.
 ...
PMID:Photooxidation of troglitazone, a new antidiabetic drug. 862 53

To examine the impact of insulin resistance on the insulin-dependent and insulin-independent portions of muscle glycogen synthesis during recovery from exercise, we studied eight young, lean, normoglycemic insulin-resistant (IR) offspring of individuals with non-insulin-dependent diabetes mellitus and eight age-weight matched control (CON) subjects after plantar flexion exercise that lowered muscle glycogen to approximately 25% of resting concentration. After approximately 20 min of exercise, intramuscular glucose 6-phosphate and glycogen were simultaneously monitored with 31P and 13C NMR spectroscopies. The postexercise rate of glycogen resynthesis was nonlinear. Glycogen synthesis rates during the initial insulin independent portion (0-1 hr of recovery) were similar in the two groups (IR, 15.5 +/- 1.3 mM/hr and CON, 15.8 +/- 1.7 mM/hr); however, over the next 4 hr, insulin-dependent glycogen synthesis was significantly reduced in the IR group [IR, 0.1 +/- 0.5 mM/hr and CON, 2.9 +/- 0.2 mM/hr; (P < or = 0.001)]. After exercise there was an initial rise in glucose 6-phosphate concentrations that returned to baseline after the first hour of recovery in both groups. In summary, we found that following muscle glycogen-depleting exercise, IR offspring of parents with non-insulin-dependent diabetes mellitus had (i) normal rates of muscle glycogen synthesis during the insulin-independent phase of recovery from exercise and (ii) severely diminished rates of muscle glycogen synthesis during the subsequent recovery period (2-5 hr), which has previously been shown to be insulin-dependent in normal CON subjects. These data provide evidence that exercise and insulin stimulate muscle glycogen synthesis in humans by different mechanisms and that in the IR subjects the early response to stimulation by exercise is normal.
 ...
PMID:NMR studies of muscle glycogen synthesis in insulin-resistant offspring of parents with non-insulin-dependent diabetes mellitus immediately after glycogen-depleting exercise. 864 74

Sciatic nerve phospholipids obtained from insulin-treated streptozocin-induced diabetic, non-treated streptozocin-induced diabetic, and healthy, control male Sprague-Dawley rats after eighteen weeks of diabetes were studied by 31P NMR spectrometry. Eleven phospholipids resonances were identified as follows: Phosphatidic acid (Chemical shift, 0.30 ppm), dihydrosphingomyelin (0.13 ppm), ethanolamine plasmalogen (0.07 ppm), phosphatidylethanolamine (0.03 ppm), phosphatidylserine (-0.05 ppm), sphingomyelin (-0.09 ppm), lysophosphatidylcholine (-0.28 ppm), phosphatidylinositol (-0.30 ppm), alkylacylglycerophosphorylcholine (-0.78 ppm), choline plasmalogen (-0.80 ppm), and phosphatidylcholine (-0.84 ppm). Diabetic rats showed that phosphatidylcholine was significantly elevated (p < 0.05), and ethanolamine plasmalogen and choline plasmalogen were significantly lower when compared with both control and insulin treated rats. The choline ratio (choline-containing phospholipids over noncholine phospholipids) was significantly elevated in the diabetic group, when compared with both control and insulin-treated groups. The ethanolamine ratio (ethanolamine-containing phospholipids over nonethanolamine phospholipids) and the ratio of the ethanolamine ratio over the choline ratio, was significantly elevated in the control and the insulin-treated groups when compared with the diabetic group. The presence of phosphatidic acid and the significance in phosphatidylcholine and ethanolamine plasmalogen, suggested that insulin had a role in the phosphatidylcholine metabolism in the rat nerve.
 ...
PMID:Insulin inhibits changes in the phospholipid profiles in sciatic nerves from streptozocin-induced diabetic rats: a phosphorus-31 magnetic resonance study. 866 97

Glucose and phosphorus metabolism in mature (8-month-old) rat lenses were examined with NMR spectroscopy. Nondiabetic mature lenses contained sorbitol-3-phosphate (S3P) and fructose-3-phosphate (F3P) which were absent from young (1- to 2-month-old) normal rat lenses. The concentrations of these two phosphates can be changed through (1) diabetes induction with streptozotocin - this results in a dramatic increase in both compounds; and (2) oral dosing with a drug known to prevent sorbitol production - both metabolites disappeared. When normal mature lenses were incubated in 35.5 mM 13C1-glucose, both 13C1-lactate and 13C3-lactate were produced. Preservation of the 13C label at C1 is likely through the formation of 13C1-S3P and -F3P, which were then split through an aldolase-like mechanism into two 3-carbon compounds, one an unlabeled glycerol and the other 13C1-alpha-glycerophosphate (from S3P) and 13C1-dihydroxyacetone phosphate (from F3P). These reactions can contribute to the increase in alpha-glycerophosphate observed in both the streptozotocin-induced diabetic lenses and lenses incubated in high glucose.
 ...
PMID:The further metabolism of sorbitol-3-phosphate and fructose-3-phosphate in the mature rat lens. 872 78

Synthesis of postulated hydroxylated metabolites of gliclazide is described together with their detailed structural analysis using 1H-NMR, two-dimensional 1H-NMR, and MS to characterize the products. Metabolism of gliclazide has been investigated in the urine of nine patients of different ethnic origins receiving gliclazide therapy for the treatment of diabetes. Urine extracts were analyzed by GC/MS to quantify and identify the metabolites excreted in urine and the metabolites compared with the synthesized products. Metabolic profiles in all diabetic patients were very similar and comparable with those reported for healthy human volunteers. In addition to the expected metabolites arising from oxidation of the 4-methylphenyl ring, four isomeric hydroxylated products of the azabicyclooctyl ring were identified and the structure of a fifth isomer postulated.
 ...
PMID:Synthesis of putative metabolites and investigation of the metabolic fate of gliclazide, [1-(3-azabicyclo(3,3,0)oct-3-yl)-3-(4-methylphenylsulfonyl) urea], in diabetic patients. 882 91

Indications for treatment at the Misasa Hot Spring, a radon producing radioactive spring, include hypertension, diabetes mellitus and pain. To clarify its mechanisms of action on these conditions, we evaluated dynamic changes in blood components such as vasoactive substances after radon inhalation. Vasodilation, alleviation of diabetic symptoms and morphine-like analgesic effects were observed, suggesting that these changes constitute part of the mechanisms of the radon spring therapy on the above conditions.
Physiol Chem Phys Med NMR 1996
PMID:Experimental study of alleviation of hypertension, diabetes and pain by radon inhalation. 887 2

The insulin minisatellite of the insulin-linked polymorphic region (ILPR), a 14 base-pairs long tandem repeat of: 5'-ACAGGGGTGTGGGG-3' 3'-TGTCCCCACACCCC-5', is located 363 base-pairs upstream of the human insulin gene. A locus for insulin-dependent diabetes mellitus (IDDM) has been mapped to the ILPR. It has been shown that the ILPR is polymorphic in length and this length polymorphism is also related to the transcriptional activity of the insulin gene and the susceptibility to IDDM. Here, we attempt to decipher the role of the ILPR structure in length polymorphism and transcriptional regulation. We show by gel electrophoresis, circular dichroism (CD) and one and two-dimensional nuclear magnetic resonance spectroscopy (1D/2D NMR) that the G-rich strand of the ILPR adopts an intramolecularly folded hairpin G-quartet structure. A detailed analysis of 1D/2D NMR data of d(G4TGTG4) and d(G4TGTG4ACAG4TGTG4) enables us to define the nature of chainfolding, the stacking interaction of the G-tetrads in the stem, and the interactions of the bases in the loops. d(G4TGTG4ACAG4TGTG4) happens to be the smallest unit of the G-rich strand that can form the intramolecular hairpin G-quartet structure. For long ILPR sequences, several such hairpin G-quartet structures can be linked in space. Indeed, by an in vitro replication assay, we show the presence of such multiple hairpin G-quartet structures for the G-rich strand of the ILPR of repeat length 6. This observation suggests that the formation of multiple hairpin G-quartets may explain slippage during replication and the observed length polymorphism. From our high resolution structure, we are able to identify a set of interactions that are critical for the structure and stability of the hairpin G-quartet. Single or double mutations in the ILPR that destabilize these interactions also lower the transcriptional activity of the insulin gene. Therefore, the hairpin G-quartet structure of the ILPR has a direct correlation with the transcriptional activity of the human insulin gene.
 ...
PMID:Structure-function correlations of the insulin-linked polymorphic region. 896 3


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>