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)

Methodologies for T and B lymphocyte quantitation, lymphocyte blast transformation (LBT) and carbohydrate (CHO) metabolism are important for assessing host lymphocyte response in the clinical laboratory. Modifications of methods for each of these techniques are presented. Results from studies of normal ambulatory adults, patients with diabetes mellitus, sickle cell disease and hyperlipidemia are reported. LBT of normal lymphocytes before and after ethanol exposure are examined. LBT during pregnancy is evaluated. T cell populations are abnormally high in black diabetics and decreased in patients with sickle cell anemia. B cell subpopulations are increased in patients with sickle cell anemia. LBT responses are decreased in maturity onset diabetes, during pregnancy and in patients with sickle cell disease. Ethanol in amounts attainable during human consumption results in significantly decreased LBT response. CHO metabolism (especially hexose monophosphate shunt [HMPS] and HMPS by pentose sugar recycling) is abnormal in diabetic lymphocytes. The low HMPS activity is partially reversible by treatment with prostaglandin synthetase inhibitors. Information related to lymphocytes in normal states remains to be collected by further clinical application of these techniques of quantitation and in vitro function.
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PMID:B and T lymphocytes: quantitation, function, and clinical applicability. 696 70

In isolated rat pancreatic islets, glucose (5.6, 11.1, and 16.7 mM) significantly increased reduced glutathione (GSH) and decreased oxidized glutathione (GSSG) levels in a dose-related manner. This was paralleled by a concomitant increase of NADPH and a decrease of NADP. The change of the GSH level occurred as quickly as one minute after addition of glucose. Exogenous insulin (200, 400, and 800 microU/ml) significantly decreased islet GSH levels in the presence of 5.6 and 16.7 mM glucose and significantly inhibited the insulin-releasing effect of the thiol reagent parachloromercuribenzoate (p-CMB) and tolbutamide. These data, together with earlier observations, suggest that GSH levels in pancreatic islets are increased by glucose and decreased by exogenous insulin via their effects on the pentose phosphate shunt and NADPH. Our results are compatible with the hypothesis that glucose and exogenous insulin, by modifying the redox state of the NADPH/NADP and GSH/GSSG systems, modulate the sensitivity of the beta-cell to the insulin-triggering actions of glucose, p-CMB, and tolbutamide.
Diabetes 1980 Oct
PMID:Islet glutathione and insulin release. 700 64

The pentose phosphate pathway operates at an elevated level in rat kidney following induction of diabetes and in the compensatory hypertrophy following unilateral nephrectomy in control and alloxan-diabetic rats, as shown by the yields of 14CO2 from [1-14C]glucose, [6-14C]glucose and 3H2O yields from [2-3H]glucose. The elevated flux through the pentose phosphate pathway is correlated with the increased RNA content and weight of the kidney. The direct utilization of NADPH for reductive synthetic reactions and the potential for indirect utilization via the sorbitol route and the linked transhydrogenase reactions of the glucuronate-xylulose pathway, for NADH and ATP generation, are also discussed.
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PMID:Regulation of pathways of glucose metabolism in kidney. Specific linking of pentose phosphate pathway activity with kidney growth in experimental diabetes and unilateral nephrectomy. 716 Apr 88

Many studies have shown that the contractile response of the rat left ventricle is impaired in diabetes mellitus. Few studies have examined the acute in vivo effects of catecholamines on the right ventricle of diabetic rats. The present study investigates the acute in vivo effects of norepinephrine (100 micrograms.kg-1.h-1 continuous intravenous infusion for 15 minutes) on the function of the right and left ventricle of diabetic rats. The effects of isoproterenol (25 mg.kg-1, subcutaneously) on the activity of glucose-6-phosphate dehydrogenase, the first and rate limiting enzyme of the oxidative pentose phosphate pathway, and on adenine nucleotide biosynthesis of the diabetic heart were also examined. Diabetes mellitus was induced by a single intravenous injection of streptozotocin (60 mg.kg-1) 4 weeks before measurements. The hemodynamic measurements were made on intact, anesthetized rats with Millard ultraminiature pressure tip catheters. The basal hemodynamic measurements (left ventricular systolic pressure, diastolic aortic pressure, left ventricular dP/dtmax, right ventricular systolic pressure and right ventricular dP/dtmax) as well as glucose-6-phosphate dehydrogenase activity and adenine nucleotide biosynthesis were the same in the diabetic animals as in the controls. Heart rate was slower in the diabetics. Norepinephrine, after 15 minutes of intravenous infusion, induced a marked increase in heart rate, left ventricular dP/dtmax, right ventricular systolic pressure and right ventricular dP/dtmax; whereas left ventricular systolic pressure and diastolic aortic pressure remained unchanged. Isoproterenol caused a pronounced stimulation of both cardiac glucose-6-phosphate dehydrogenase activity (after 24 hours) and adenine nucleotide biosynthesis (after 5 hours).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The functional and metabolic responses of the heart to catecholamines are attenuated in diabetic rats. 757 10

The effects of glucose concentration on D-glucose oxidation and reduced nicotinamide adenine dinucleotide phosphate (NADPH) supply were studied during exposure of cultured human umbilical vein endothelial cells to hydrogen peroxide (H2O2). The activation of glucose oxidation via the pentose phosphate pathway (PPP), induced by exposure of cells to 200 mumol/l H2O2 for 1 h, was reduced by 50% (P < 0.01) in cells cultured for 5-7 days in 33 mmol/l D-glucose (HG) versus those cultured in 5.5 mmol/l D-glucose without (NG) or with (HR) 27.5 mmol/l D-raffinose. The intracellular NADPH content in HG cells, but not in NG or HR cells, was decreased by 42% (P < 0.01) by exposing cells to 200 mumol/l H2O2. The decrease in NADPH was dependent on D-glucose concentration in the medium and was prevented in glutathione (GSH)-depleted cells. The latter observation suggests that the decrease in NADPH is associated with activation of the GSH redox cycle. In the presence of 200 mumol/l H2O2, lactate release into the medium, NADH/NAD ratio, and phosphofructokinase activity in HG cells were 56, 53, and 68% greater, respectively, than in the NG group, which indicates that inhibition of glycolysis by H2O2 is less marked in the HG group compared with NG group. These results indicate that activation of the PPP was impaired in endothelial cells cultured under conditions of high-glucose and oxidative stress, resulting in a decreased supply of NADPH to various NADPH-dependent pathways, including the GSH redox cycle.
Diabetes 1995 May
PMID:Impaired activation of glucose oxidation and NADPH supply in human endothelial cells exposed to H2O2 in high-glucose medium. 772 9

The Maillard or browning reaction between reducing sugars and proteins contributes to the chemical aging of tissue proteins in vivo and to the accelerated aging of proteins in diabetes. To identify reactive carbohydrate intermediates formed in the Maillard reaction under physiological conditions, we studied the decomposition of the model Amadori compound, N alpha-formyl-N epsilon-fructoselysine (fFL) and of Amadori compounds on glycated collagen at pH 7.4 and 37 degrees C. Because of effects of buffer and oxidative conditions on the decomposition of Amadori compounds, the kinetics and products of decomposition were studied in varying phosphate concentrations and in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (Hepes) buffer under both aerobic and anaerobic conditions. The half-life of fFL was significantly shorter in phosphate, compared to Hepes buffer, and under aerobic, compared to anaerobic, conditions. The decomposition of both fFL and Amadori adducts on glycated collagen was accelerated by increasing the phosphate concentration and/or pH. Glucose and mannose were identified as major products formed by reversal of the Amadori rearrangement, along with tetroses, pentoses, and 3-deoxyglucosone, formed by reverse aldol, rearrangement, and hydrolysis reactions. The tetrose and pentose products included both aldose and ketose sugars. These same products were also formed in similar yields on decomposition of Amadori adducts on glycated collagen in vitro. The spontaneous decomposition of Amadori compounds to more reactive sugars in vivo, including tetroses, pentoses, and 3-deoxyglucosone, provides a mechanism for generating reactive intermediates under physiological conditions and for propagating damage to protein as a result of glycation of proteins by glucose in vivo.
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PMID:Formation of reactive intermediates from Amadori compounds under physiological conditions. 784 Jun 65

The effect of alloxan-induced diabetes on CuZn- and Mn-superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) activities, as well as the content of thiobarbituric acid reactive substances (TBARs) were examined in rat lymphoid organs (mesenteric lymph nodes (MLN), thymus and spleen) and, for comparison, red and white muscle fibres. The capacity for generation of reduced equivalents was also evaluated by measuring the activities of glucose-6-phosphate dehydrogenase (pentose-phosphate pathway-cytosol) and citrate synthase (Krebs cycle-mitochondria). Diabetes raised the capacity for the generation of reducing equivalents in the lymphoid organs: in the mitochondria of the thymus and spleen and in the cytosol of the mesenteric lymph nodes and thymus. In muscles, diabetes reduced CuZn-SOD activity in soleus and raised the activity in gastrocnemius, and depressed the activities of catalase in soleus and of glutathione peroxidase in both soleus and gastrocnemius. In relation to the lymphoid organs, the spleen showed a decrease in the antioxidant enzyme activities (except for glutathione peroxidase), whereas the thymus showed an increased level (except for Mn-SOD), and the MLN presented a reduction in Mn-SOD and catalase activities and an increase in GPX activity caused by diabetes. The content of TBARs in the tissues followed the changes in GPX activity inversely: i.e. a decrease in the lymphoid organs (except in the spleen) and an increase in the muscles of diabetic rats compared with the control group. All these changes found in diabetic rats were reversed by insulin treatment and were not modified by the normalization of glycaemia.
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PMID:Superoxide dismutase, catalase and glutathione peroxidase activities in the lymphoid organs of diabetic rats. 796 75

The cellular redox state is altered in a number of pathological conditions, including various forms of glomerular injury and diabetes. For example, glucose, via the pentose phosphate pathway generates NADPH, which maintains glutathione (GSH) (part of a major intracellular reducing system) in its reduced state. GSH in turn influences the activity of transcription factors on gene expression. We therefore examined whether changes in cellular GSH influence total collagen synthesis and mRNA levels for collagen I, collagen IV and TGF-beta in SV-40 transformed mouse mesangial cells (MC) maintained in either 5 or 25 mM glucose media. Total intracellular GSH was increased by N-acetylcysteine (NAC; 10 mM) or decreased with the GSH synthesis inhibitor buthionine sulfoximine (BSO; 0.2 mM) in MC. NAC increased 3H-proline incorporation into collagenase-sensitive protein while BSO decreased it under both glucose conditions. The presence of BSO did not reverse the increased collagen synthesis seen in the NAC stimulated cells. Northern blot analysis showed increased mRNA levels for collagen I, collagen IV and TGF-beta in cells grown in high glucose (25 mM). NAC increased the mRNA for all three compounds while BSO alone had no effect on these mRNA levels. However, BSO reversed the increased mRNA levels for collagen I, IV and TGF-beta seen in the presence of NAC. These findings suggest that the cellular redox state may influence gene transcription in MC, and may have implications in explaining injury-associated alterations of mesangial matrix generation.
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PMID:Intracellular glutathione influences collagen generation by mesangial cells. 796 50

The acute effects of streptozotocin-induced diabetes on several parameters of glucose metabolism were investigated in rat peritoneal macrophages. These cells accumulated in vitro about twofold more fructose 2,6-bisphosphate in the presence of increasing glucose concentration than cells from normal rats, and an increased production of lactate was observed. Phosphofructokinase-1, phosphofructokinase-2, hexokinase, and pyruvate kinase activities were increased in cells from diabetic rats compared with those from normal rats. Transport of 2-deoxy-D-glucose was increased in cells from diabetic rats. [U-14C]Glucose incorporation into glycogen was also increased in cells from diabetics and the 14CO2 liberation was less than in cells from normal animals. Moreover, macrophages from diabetics did not possess a more active pentose phosphate pathway (measure with [1-14C]glucose oxidation) nor a greater production of superoxide anion (index of activation of macrophages) than in cells from normal animals.
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PMID:Streptozotocin-induced diabetes increases fructose 2,6-bisphosphate levels and glucose metabolism in rat macrophages. 812 90

Streptozotocin diabetes induces a 4-fold increase in the maximal velocity of inner medullary aldose reductase as determined in vitro but increases sorbitol synthesis in intact inner medullary collecting duct (IMCD) cells only 1.3-fold. In order to resolve this discrepancy we investigated the importance of intracellular factors in controlling the role of cellular sorbitol synthesis. These factors include glucose concentration, sorbitol concentration, the activity of the NADPH-regenerating pentose phosphate pathway, intracellular NADP and NADPH content, and intracellular reduced (GSH) and oxidized glutathione (GSSG). It was found that the apparent Km of cellular sorbitol production for glucose was identical in control and diabetic rats (56 +/- 18 vs. 59 +/- 14 mmol/l D-glucose), whereas Vmax increased by 31% in diabetes. In inner medullary collecting duct cells of diabetic rats containing 146 +/- 5 mumol sorbitol/g protein, sorbitol synthesis was slightly lower (-15%), compared to cells which had been sorbitol-depleted prior to the experiment (87 +/- 4 mumol sorbitol/g protein). However, no inhibitory effect of sorbitol (up to 200 mmol/l) was observed on aldose reductase activity in vitro. In diabetic rats the content of NADPH was about 32% lower than in the control rats (3.8 +/- 0.3 vs. 5.6 +/- 0.4 mumol/g protein) and the ratio of NADPH/NADP was decreased from 25.6 +/- 5.1 to 8.6 +/- 1.7. In homogenates of the inner medulla the activity of 6-phospho-gluconate dehydrogenase (EC 1.1.1.43) was identical in both experimental groups, so the pentose phosphate shunt seems to be unaltered. GSH content in diabetic rats was also diminished (4.02 +/- 0.67 mumol/g protein vs. 7.41 +/- 0.5 mumol/g protein) and the GSH/GSSG ratio fell from 92.6 to 57.4. In enzyme tests in vitro an apparent Km of 7.3 +/- 1.9 mumol/l of the aldose reductase for NADPH was found; NADP acted as competitive inhibitor with an apparent K(i) of 183 +/- 31 mumol/l. Aldose reductase activity was also found to be strongly inhibited by the SH-group reagent p-chloromercurybenzoesulfonate (apparent K(i) = 0.85 x 10(-6) mol/l). Combining the results obtained on the properties of the aldose reductase in vitro and the observation made in the intact cells, the investigators suggest that the decrease in NADPH/NADP ratio, as well as changes in the redox state in the cells of diabetic animals, can play a significant role in the control of sorbitol synthesis.
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PMID:Control of sorbitol metabolism in renal inner medulla of diabetic rats: regulation by substrate, cosubstrate and products of the aldose reductase reaction. 824 Dec 88


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