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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the presence of glucose (2 mg/ml), leucine (10 mM) noticeably increased islets' NADPH contents as well as the NADPH:NADP ratio; the changes occurred as soon as 1 min after its addition. NADH concentrations were also increased by leucine. The NADPH:NADP ratio as well as insulin release stimulated by glucose plus leucine were markedly decreased by methylene blue. The thiol oxidants diamide and tert-butyl hydroperoxide also inhibited insulin secretion in response to glucose plus leucine. Employing the perfused pancreas technique, the insulin-releasing action of p-chloromercuribenzoate was further enhanced by leucine. The combined effects were inhibited by tert-butyl hydroperoxide, however. Our data suggest that the insulin-releasing action of leucine depends on the islets' NADPH and reduced glutathione (GSH); in addition, leucine may contribute to insulin secretion by increasing the islet NADPH:NADP ratio and the NADH:NAD ratio. From the data, we assume that the observed increase of NADPH may lead via GSH to an increase in the number of such thiol groups in the beta-cell membrane, which are believed to be related to stimulation of insulin release and, thus, to increase the sensitivity of the beta-cell to stimulation by glucose and/or leucine.
Diabetes 1979 Jun
PMID:Effect of leucine on the pyridine nucleotide contents of islets and on the insulin released--interactions in vitro with methylene blue, thiol oxidants, and p-chloromercuribenzoate. 3 18

Previous studies had shown that administration of streptozotocin to rats produces both diabetes and hemolysis and that both could be ameliorated by prior injections of diazoxide. Thus, it appeared pertinent to define the effect of streptozotocin on the red cell. In the present studies, streptozotocin administered in vivo to rats produced a rapid fall in red-cell-reduced glutathione. This effect was duplicated in vitro in incubated human red cells. Furthermore, it was demonstrated that glucose loading prior to bleeding modified the in-vitro red-cell GSH response to streptozotocin and that preincubation of red cells from fasted individuals with glucose, nicotinamide, and epinephrine (but not nicotinic acid) protected against the subsequent effect of streptozotocin on RBC GSH. The pattern of the RBC GSH response under each of these conditions is that which occurs in response to challenge with an oxidant, that is, with appropriate protection, oxidation stress produces an acute rise rather than falll in gsh. further, when glucose was present through both preincubation and test periods (i.e., in presence of streptozotocin) a third pattern of GSH response was observed--no change. The data are compatible with the postulate that the cytotoxic action of streptozotocin is dependent, in part, on an oxidant effect, and that glucose may protect through at least two mechanisms, that adrenergic stimulation can enhance protective mechanisms against redox insults and so contribute to maintenance of cell viability.
Diabetes 1976 Mar
PMID:Effect of streptozotocin on red-blood-cell-reduced glutathione: modification by glucose, nicotinamide, and epinephrine. 13 Feb 72

The degradation of insulin by isolated rat liver cells has been studied. The phenomenon is time- and temperature-dependent. After sixty minutes' exposure to 1.5 times 10-6 cells/ml, about 50 per cent, 15 per cent, and less than 5 per cent of insulin at 1.5 muM. are degraded at 37 degrees C., 20 degrees, and 0 degrees C., respectively. The methods used to measure the hormone degradation effect the apparent Vmax. Higher values of Vmax are found when radioimmunoassay rather than precipitation by trichloracetic acid and absorption to talc is used. However, the apparent Km. (0.27 muM) is virtually the same with any of methods used. N-ethyl-maleimide and Trasylol are potent inhibitors, whereas GSH increases the hormone degradation. Proinsulin acts as competitive inhibitor (apparent Ki equals 0.35 muM.). Gel filtration patterns of incubation supernates suggest that several enzymatic systems may be operative in the degradation of insulin by the liver cells. Glutathione-insulin-transhydrogenase is suggested by the appearance of a component that has the same elution volume as the A chain, but the inhibitory effects of trasylol on insulin degradation, as well as qualitative and quantitative similarities with insulin proteases, suggest that a proteolytic similiarities with insulin proteases, suggest that a proteolytic mechanism is involved. The insulin-degrading system in isolated liver cells closely resembles that observed in purified liver plasma membranes and in the isolated perfused liver. Such similarities stress the possible significance of the degradation process in the regulation of insulin action. These studies are also important for the quantitative analysis of insulin interaction with its specific receptors in isolated liver cells.
Diabetes 1975 Jun
PMID:Degradation of insulin by isolated rat liver cells. 16 96

In hagfish islet parenchyma, consisting practically only of insulin-producing B-cells and agranular B-cell precursors, the contents of glutathione (GSH) and total protein-free thiols (NPSH) were determined on micro-dissected islet lobules. GSH was found to be of the same order of magnitude (22-25 mg/100 g wet weight) as in the islet parenchyma of a previously studied teleost fish and of some mammals, including man. However, the NPSH was found to be considerably higher in the islet lobules of the hagfish than in the teleostean islet parachyma. As in both teleost fish and mammals, GSH made up most of the NPSH in the hagfish erythrocytes, myocardium, and skeletal musculature. This discrepancy between hagfish islet parenchyma and other tissues indicates that the non-GSH portion of NPSH may be of particular significance for the insulin-producing B-cells. By means of flameless atomic absorption spectrophotometry the contents of zinc, cobalt, and manganese were determined in micro-dissected hagfish islet lobules. Neither zinc, nor cobalt, occurred in significantly higher concentrations in the islet parenchyma than in the liver or the skeletal musculature. Only manganese was found in somewhat higher amounts in the islet lobules than in the other tissues, but the contents were still low. The results indicate that none of the three heavy metals play any important role in the synthesis, storage, or release of insulin in the hagfish. The significance of this in relation to the prevailing hypotheses regarding the pathogenesis of alloxan diabetes is discussed.
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PMID:Microchemical assays of glutathione, zinc, cobalt and manganese in micro-dissected areas of the endocrine pancreas in the hagfish, Myxine glutinosa. 33 56

Interactions between manganese (Mn) deficiency and streptozotocin (STZ)-diabetes with respect to tissue antioxidant status were investigated in male, Sprague-Dawley rats. All rats were fed either a Mn-deficient (1 ppm) or a Mn-sufficient (45 ppm) diet for 8 wk. Diabetes was then induced by tail-vein injection of STZ (60 mg/kg body weight), after which the rats were kept for an additional 4 or 8 wk. The control groups comprised rats not injected with STZ and fed either Mn-deficient or Mn-sufficient diets for a total of 12 wk. The Mn-deficient diet decreased the activities of manganese superoxide dismutase (MnSOD) in kidney and heart, and of copper-zinc superoxide dismutase (CuZnSOD) in kidney, in the non-diabetic animals. In the diabetic rats, the Mn-deficient diet induced more pronounced decreases in activities of these same enzymes, and also increased liver MnSOD activity. Plasma and hepatic vitamin E levels increased progressively with the duration of diabetes, independent of dietary Mn intake. Lipid peroxidation, as measured by H2O2-induced production of thiobarbituric acid reactive substances in erythrocytes, also increased, concomitant with decreased liver and kidney glutathione (GSH) levels. These findings demonstrate for the first time and interactive effective between Mn deficiency and STZ-diabetes, resulting in amplification of tissue antioxidant changes seen with either Mn deficiency or STZ-diabetes alone. This effect of Mn deprivation in experimental diabetes suggests a physiological role for Mn as an antioxidant nutrient.
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PMID:Tissue antioxidant status in streptozotocin-induced diabetes in rats. Effects of dietary manganese deficiency. 128 89

Erythrocyte sodium pump activity, osmotic fragility, and thiol status were measured in genetically hyperglycemic (db/db) mice and compared with their nondiabetic littermates (db/m). The data showed no major differences in these parameters. However, erythrocytes from streptozotocin (Stz)-induced diabetic rats had significantly lower activity of sodium pump and thiols with an almost fourfold increase in osmotic fragility as compared with erythrocytes from nondiabetic rats. Sorbinil (an aldose reductase inhibitor) treatment of Stz-diabetic rats normalized all these lesions, suggesting a key role for polyol pathway. However, sorbitol levels in erythrocytes from db/db and db/m mice were undetectable. The data suggest that in db/db mice, the relative lack of polyol pathway, a potential consumer of NADPH, may provide erythrocytes with optimal NADPH for glutathione reductase system, thus maintaining normal GSH levels even at the height of hyperglycemia. Thus, the genetically hyperglycemic mice may serve as a useful model to study diabetes related complications without involving polyol pathway.
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PMID:Erythrocyte sodium-potassium ATPase activity and thiol metabolism in genetically hyperglycemic mice. 131 May 17

Several components of the erythrocyte-dependent glutathione redox system (reduced glutathione, GSH; oxidized glutathione, GSSG; glutathione peroxidase, GSH-Px; glutathione reductase, GSH-Red) were determined in patients with types I and II diabetes mellitus (DM). All groups studied were male subjects: G1, 20 young healthy individuals (aged 23.7 +/- 4.2 years); G2, 15 young insulin-treated type I DM patients; G3, 20 older insulin-treated type II DM patients; G4, 21 older oral hypoglycemic agent-treated type II DM patients; G5, 28 aged healthy individuals (aged 68.9 +/- 11.5 years). There were no differences between G1 and G2, G3 or G4 regarding erythrocyte GSH, GSSG, and GSH-Red (without FAD) levels. GSH-Px activity was significantly lower in G2 when compared to G1 (15.2 +/- 4.9 vs 20.6 +/- 6.6 IU/g Hb). The GSH-Red and GSH-Px activities and GSH levels were significantly higher in G3 (4.6 +/- 1.7 IU/g Hb, 20.2 +/- 8.7 IU/g Hb and 3.5 +/- 1.3 microM/g Hb) and G4 (5.0 +/- 2.2 IU/g Hb, 16.9 +/- 6.1 IU/g Hb and 5.0 +/- 2.3 microM/g Hb) when compared to G5 (3.4 +/- 0.9 IU/g Hb, 12.0 +/- 3.6 IU/g Hb and 2.3 +/- 0.9 microM/g Hb). The findings suggest that treatment of DM can stimulate the redox activity of red blood cells in aged subjects.
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PMID:Influence of diabetes mellitus on the glutathione redox system of human red blood cells. 134 8

The defense system of aortic endothelial cells against oxidative stress was studied in alloxan-induced diabetic rabbits, and the effect of insulin on the antioxidant activities was estimated. Endothelial cells were prepared from 10 diabetic rabbits, 18 diabetic rabbits treated with insulin, and 10 age-matched controls after 17 days of diabetes. These cells were used for the estimation of glutathione (GSH) levels and its related enzyme activities. The antioxidant activities in these endothelial cells from diabetic rabbits were compared with those from control subjects. The concentration of GSH decreased in diabetic rabbits (1.6 +/- 0.2 nmol/mg protein [mean +/- SD] v 3.7 +/- 0.6 nmol/mg protein). Decreases in the activities of Cu, Zn-superoxide dismutase (Cu,Zn-SOD) (62.7 +/- 11.0 U/mg protein v 172.9 +/- 20.2 U/mg protein), catalase (7.6 +/- 2.1 U/mg protein v 12.3 +/- 3.2 U/mg protein), and GSH peroxidase (134.0 +/- 27.0 mU/mg protein v 179.1 +/- 26.2 mU/mg protein) were observed. The activities of other GSH-related enzymes such as GSH S-transferase or GSH reductase did not change in endothelial cells from diabetic rabbits. Most of these antioxidant activities were prevented when diabetic rabbits were treated with insulin (1 to 2 U/kg/d). These antioxidant activities were also determined in the diabetic liver and kidney. Similar decreases in the cellular defense activities and prevention of the decrease in activities by insulin were observed in the diabetic liver, while these antioxidant enzyme activities in the kidney were resistant to diabetic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of insulin on impaired antioxidant activities in aortic endothelial cells from diabetic rabbits. 140 92

The levels of catalase (CAT), glutathione-s-transferase (GST), reduced glutathione (GSH) and oxidised glutathione (GSSG) were measured in red blood cells from control (C) and diabetic rats (D). Diabetes was induced by alloxan administration and diabetic rats were treated with insulin (D+I) and thyroxine (D+T4). On the third day of insulin withdrawal the CAT activity increased significantly. The GST activity showed an increase in D and D+I for one week, thyroxine treatment to D rats resulted in maintaining the GST activity at control levels. The levels of GSH and GSSG increased in D red cells after one week of insulin withdrawal but later, the GSH level was below the control level while the GSSG was at its control level. Insulin treatment to D rats did not reverse GSH level to control initially but controlled it at a later stage. Thyroxine, though, reversed GSH levels but enhanced GSSG in D rat red cells.
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PMID:Effect of insulin and thyroxine on catalase, glutathione-s-transferase, GSH and GSSG in alloxan diabetic rat red cells. 141 13

Abnormalities of both free radical activity and ascorbic acid metabolism have been documented in diabetes, but their biological basis is unclear and their relationship unstudied in any detail. This study was designed to compare changes in antioxidant status and free radical reactions in a group of elderly diabetic patients (with and without retinopathy) with those in a group of age-matched control subjects. No significant differences in thiobarbituric acid (TBA) reactivity, red cell glutathione (GSH) concentrations or diene conjugates (DC) between patients and controls were seen despite significant depletion of ascorbic acid in patients with diabetes, especially in those with retinopathy. The results emphasise the present-day difficulties of measuring free radical activity and demonstrate a marked abnormality in ascorbic acid metabolism in diabetes.
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PMID:An investigation of the relationship between free radical activity and vitamin C metabolism in elderly diabetic subjects with retinopathy. 142 25


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