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

Results of the initial clinical evaluation in 20 human subjects of a subcutaneously implanted microsensor-based amperometrically glycemia-monitoring system, carried out between April 1994 and June 1995, are reported. The system was based on the electrical connection ("wiring") of the reaction centers of glucose oxidase to a gold electrode and on elimination of the chemicals that interfere with glucose monitoring through their horseradish peroxidase-catalyzed oxidation by internally generated hydrogen peroxide. The sensor was finer than a 29-gauge needle and had no leachable components. Because of its high selectivity for glucose, the sensor output was virtually nil at zero glucose level. This enables prompt "one-point" in vivo calibration of the sensor with a single blood glucose sample. Microsensors were subcutaneously implanted in ten nondiabetic and ten insulin-dependent diabetes mellitus (IDDM) volunteers. All subjects underwent standard meal tests and intravenous glucose-tolerance tests (IVGTT) in addition to hourly plasma glucose measurements. The sensor signals were continuously recorded, and the glucose concentration estimates were derived by calibrating the sensor using a single blood sample (one-point calibration). Regression analysis revealed that the sensor-estimated glucose concentrations were linearly related to the plasma glucose concentrations (r2 = 0.75) over a wide glucose concentration range (2-28 mmol/L) (sensor estimate = plasma 0.96 + 0.26 mmol/L). The difference between the estimated and actual glucose concentration was -0.13+/-0.23 mmol/L [mean +/-95% confidence interval (CI), n = 546], and 95% of the estimates fell in clinically acceptable zones of the Clarke error grid. The sensing delay time was 10.4+/-2.3 min as measured by the IVGTT. The subjects reported no discomfort associated with wearing the sensors.
J Diabetes Complications
PMID:Initial evaluation of a 290-microm diameter subcutaneous glucose sensor: glucose monitoring with a biocompatible, flexible-wire, enzyme-based amperometric microsensor in diabetic and nondiabetic humans. 987 61

In a recent study we have demonstrated that 3T3-L1 adipocytes exposed to low micromolar H2O2 concentrations display impaired insulin stimulated GLUT4 translocation from internal membrane pools to the plasma membrane (Rudich, A., Tirosh, A., Potashnik, R., Hemi, R., Kannety, H., and Bashan, N. (1998) Diabetes 47, 1562-1569). In this study we further characterize the cellular mechanisms responsible for this observation. Two-hour exposure to approximately 25 microM H2O2 (generated by adding glucose oxidase to the medium) resulted in disruption of the normal insulin stimulated insulin receptor substrate (IRS)-1 and phosphatidylinositol (PI) 3-kinase cellular redistribution between the cytosol and an internal membrane pool (low density microsomal fraction (LDM)). This was associated with reduced insulin-stimulated IRS-1 and p85-associated PI 3-kinase activities in the LDM (84 and 96% inhibition, respectively). The effect of this finding on the downstream insulin signal was demonstrated by a 90% reduction in insulin stimulated protein kinase B (PKB) serine 473 phosphorylation and impaired activation of PKBalpha and PKBgamma. Both control and oxidized cells exposed to heat shock displayed a wortmannin insensitive PKB serine phosphorylation and activity. These data suggest that activation of PKB and GLUT4 translocation are insulin signaling events dependent upon a normal insulin induced cellular compartmentalization of PI 3-kinase and IRS-1, which is oxidative stress-sensitive. These findings represent a novel cellular mechanism for the induction of insulin resistance in response to changes in the extracellular environment.
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PMID:Oxidative stress disrupts insulin-induced cellular redistribution of insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3-L1 adipocytes. A putative cellular mechanism for impaired protein kinase B activation and GLUT4 translocation. 1018 55

The protective effect of taurine in model in vitro diabetic cataract and the mechanism of this effect were investigated in isolated rat lenses. Isolated rat lenses were incubated in medium 199 in elevated glucose (55.6 m m) with taurine (5 m m). Taurine concentrations in the lenses were determined by amino acid analysis. Accumulative leakage of the intracellular enzyme lactate dehydrogenase (LDH) was used to estimate damage to the lens, as previously reported. In the clear lenses, prior to vacuole formation, after 1 or 2 days of incubation, the taurine and amino acids in lenses decreased progressively in concentration. In lenses incubated with 5 m m taurine, the level of taurine was increased towards that of control lenses. In taurine-treated lenses LDH leakage was significantly decreased, and lens clarity was maintained, similarly to that found previously for vitamin C and lipoic acid. To test whether taurine has similar antioxidant activity, we tested its ability to decrease luminol luminescence generated by (1) superoxide from hypoxanthine/xanthine oxidase and (2) peroxide from diluted glucose/glucose oxidase. For either superoxide or peroxide, the luminescence was decreased to zero, as a function of increasing taurine concentration, at 30 m m, approximately the physiological concentration of taurine in the lens. Spin trapping confirmed that taurine scavenged superoxide. This is consistent with a role for taurine as an important antioxidant protecting the lens against oxidative insults. Amino acids also had antioxidant activity in this assay, and as a group, when all activities were summed, their loss also contributed significantly to the antioxidant loss. Taken in conjunction with Wolff and Crabbe's observation of increased free radical generation by glucose auto-oxidation in diabetes, this suggests a push-pull mechanism for increased oxidative stress in diabetic cataract, involving both increased free radicals and decreased radical scavenging antioxidants.
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PMID:Modelling cortical cataractogenesis 22: is in vitro reduction of damage in model diabetic rat cataract by taurine due to its antioxidant activity? 1047 37

In a community based survey of gestational diabetes in 18 rural villages of the eastern zone of Tigray administrative region, northern Ethiopia, a total of 890 pregnant women with gestational age of 24 weeks and above were examined for gestational diabetes mellitus based on WHO criteria. A 75 gm oral glucose tolerance test was performed on each subject with measurement of glucose at 0 and 2 h. Blood glucose was determined by glucose oxidase method using capillary blood (Accutrend alpha, Boehringer Mannheim). The mean age of the mothers was 27.4 +/- 7.1 years. Forty four percent of the subjects were multiparas. The prevalence rate of gestational diabetes mellitus was found to be 3.7% (95% CI 2.5-4.9). The mean blood glucose 2 h after glucose load in those pregnant diagnosed to have gestational diabetes mellitus was 154.6 +/- 14.4 mg/dl (J.W. Rich-Edwards, G.A. Colditz, M.J. Stampfer, W.C. Willett, M.W. Gillman, C. Hennekens, F.E. Speizer, J.E. Manson, Birth weight and the risk for type 2 diabetes mellitus in adult women, Annu. Intern. Med. 130 (1999) 278-284). The prevalence of gestational diabetes mellitus in this region of the country is high as compared to other parts of Africa. The possible role and contribution of exposure of the general population in this area to chronic malnutrition as a result of prolonged famine, drought and war, to the high prevalence of gestational diabetes mellitus warrants further study.
Diabetes Res Clin Pract 1999 Dec
PMID:Prevalence of gestational diabetes mellitus in rural pregnant mothers in northern Ethiopia. 1062 91

The Diabetes Control and Complications Trial has conclusively demonstrated that improved metabolic control leads to reduction in the rate of microvascular complications of diabetes. In order to allow patients to achieve improved metabolic control, much research has focused on improved methods of glucose monitoring and more physiologic ways of insulin delivery. The 2 most promising methods of minimally invasive blood glucose monitoring are the Glucowatch, using the technique of reverse iontophoresis to measure interstitial fluid glucose levels every twenty minutes and an implantable sensor, in which a catheter resembling that used for insulin delivery through a pump is impregnated with glucose oxidase at the tip. This device monitors blood sugars every few minutes, but like a holter monitor, must be downloaded in the physician's office. Still under development are (1) implantable subcutaneous sensors with a high and low blood glucose alarm and (2) sensors in which the patient will be able to download the data using a home PC. Advances in insulin delivery have included the availability of new insulin analogs which more closely simulate endogenous insulin release, with rapid acting analogs simulating the increase in insulin production that normally occurs after meals. Phase III clinical trials are in progress of a long-acting basal insulin without peak actions to simulate the low dose continuous production of the insulin which normally inhibits hepatic glucose production. In addition, use of the insulin pump has increased markedly since publication of the DCCT with the greatest increase being among adolescents. In addition to advances in treatment of diabetes, research has continued on curing the disease using islet cell transplantation and preventing the disease with agents such as insulin (DPT-1 Trial) and nicotinamide (ENDIT). This article provides an overview of recent advances in diabetes management and prevention.
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PMID:New developments in type 1 (insulin-dependent) diabetes. 1082 72

Glucocorticoids reportedly induce insulin resistance. In this study, we investigated the mechanism of glucocorticoid-induced insulin resistance using 3T3-L1 adipocytes in which treatment with dexamethasone has been shown to impair the insulin-induced increase in glucose uptake. In 3T3-L1 adipocytes treated with dexamethasone, the GLUT1 protein expression level was decreased by 30%, which possibly caused decreased basal glucose uptake. On the other hand, dexamethasone treatment did not alter the amount of GLUT4 protein in total cell lysates but decreased the insulin-stimulated GLUT4 translocation to the plasma membrane, which possibly caused decreased insulin-stimulated glucose uptake. Dexamethasone did not alter tyrosine phosphorylation of insulin receptors, and it significantly decreased protein expression and tyrosine phosphorylation of insulin receptor substrate (IRS)-1. Interestingly, however, protein expression and tyrosine phosphorylation of IRS-2 were increased. To investigate whether the reduced IRS-1 content is involved in insulin resistance, IRS-1 was overexpressed in dexamethasone-treated 3T3-L1 adipocytes using an adenovirus transfection system. Despite protein expression and phosphorylation levels of IRS-1 being normalized, insulin-induced 2-deoxy-D-[3H]glucose uptake impaired by dexamethasone showed no significant improvement. Subsequently, we examined the effect of dexamethasone on the glucose uptake increase induced by overexpression of GLUT2-tagged p110alpha, constitutively active Akt (myristoylated Akt), oxidative stress (30 mU glucose oxidase for 2 h), 2 mmol/l 5-aminoimidazole-4-carboxamide ribonucleoside for 30 min, and osmotic shock (600 mmol/l sorbitol for 30 min). Dexamethasone treatment clearly inhibited the increases in glucose uptake produced by these agents. Thus, in conclusion, the GLUT1 decrease may be involved in the dexamethasone-induced decrease in basal glucose transport activity, and the mechanism of dexamethasone-induced insulin resistance in glucose transport activity (rather than the inhibition of phosphatidylinositol 3-kinase activation resulting from a decreased IRS-1 content) is likely to underlie impaired glucose transporter regulation.
Diabetes 2000 Oct
PMID:Dexamethasone-induced insulin resistance in 3T3-L1 adipocytes is due to inhibition of glucose transport rather than insulin signal transduction. 1101 54

A study was made on the association among 2-h plasma glucose (PG) in oral glucose tolerance test (OGTT), fasting plasma glucose (FPG) using correlation and regression equation. Subjects were 13174 OGTT examinees tested between 1980 and 1998. Blood glucose was determined by the glucose oxidase method and glycated hemoglobin (HbA1c) by the HPLC method. As for correlation between 2-h PG and FPG, regression equation of the <60 year group was y=57.1+0.336x (r=0.866, P<0.0001) and that of the >==60 year group was y=61.5+0.286x (r=0.814, P<0. 0001). FPG was calculated at 124.3 in the <60 year group and 118.7 mg/dl in the >==60 year group for 2-h PG of 200 mg/dl, 2-h PG were calculated at 199.5 and 210.7 mg/dl for FPG of 126 mg/dl, respectively. In the <60 year group, FPG were calculated at 121.7 and 124.4 mg/dl and 2-h PG at 193.2 and 199.3 mg/dl for HbA1c of 6.0 and 6.1%, respectively. As for associations between HbA1c and FPG or 2-h PG being high correlation, it is possible to estimate a prevalence of DM in a group using HbA1c>==6.1%. High correlations were demonstrated among all the three measures; FPG, 2-h PG, HbA1c. If 2-h PG is used in diagnosing diabetes mellitus, an FPG of 126 mg/dl proposed by ADA and World Health Organization (WHO) as a diagnostic level of FPG is an acceptable value for the Japanese.
Diabetes Res Clin Pract 2000 Dec
PMID:Correlation among fasting plasma glucose, two-hour plasma glucose levels in OGTT and HbA1c. 1110 37

A miniature needle-type sensor suitable for the simultaneous amperometric monitoring of glucose and insulin is described. The integrated microsensor consists of dual (biologically and chemically) modified carbon-paste working electrodes inserted into a 14-guage needle. The glucose probe is based on the biocatalytic action of glucose oxidase, and the insulin one relies on the electrocatalytic activity of ruthenium oxide. The analytical performance of the dual sensor is assessed under flow injection conditions. The needle dual detector exhibits a very rapid response to dynamic changes in the concentrations of glucose and insulin. No apparent cross reactivity is observed in mixtures containing millimolar glucose levels and nanomolar insulin concentrations. The response is highly linear (to at least 1000 nM insulin and 14 mM glucose) and reproducible (RSD = 2.6-4.1%). The combination microsensor holds great promise for real-time measurements of the insulin/glucose ratio and for improved management of diabetes.
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PMID:Needle-type dual microsensor for the simultaneous monitoring of glucose and insulin. 1124 2

In diabetic patients, alpha-lipoic acid (LA) improves skeletal muscle glucose transport, resulting in increased glucose disposal; however, the molecular mechanism of action of LA is presently unknown. We studied the effects of LA on basal and insulin-stimulated glucose transport in cultured rat L6 muscle cells that overexpress GLUT4. When 2-deoxy-D-glucose uptake was measured in these cells, they were more sensitive and responsive to insulin than wild-type L6 cells. LA, at concentrations < or = 1 mmol/l, had only small effects on glucose transport in cells not exposed to oxidative stress. When cells were exposed to glucose oxidase and glucose to generate H2O2 and cause oxidative stress, there was a marked decrease in insulin-stimulated glucose transport. Pretreatment with LA over the concentration range of 10-1,000 pmol/l protected the insulin effect from inhibition by H2O2. Both the R and S isomers of LA were equally effective. In addition, oxidative stress caused a significant decrease (approximately 50%) in reduced glutathione concentration, along with the rapid activation of the stress-sensitive p38 mitogen-activated protein kinase. Pretreatment with LA prevented both of these events, coincident with protecting insulin action. These studies indicate that in muscle, the major site of insulin-stimulated glucose disposal, one important effect of LA on the insulin-signaling cascade is to protect cells from oxidative stress-induced insulin resistance.
Diabetes 2001 Feb
PMID:Protection against oxidative stress-induced insulin resistance in rat L6 muscle cells by mircomolar concentrations of alpha-lipoic acid. 1127 54

In experimental models of diabetes, glucose levels in plasma and blood are commonly determined by colorimetric assay and by automated analyzers based on the glucose oxidase conversion of glucose and O2 to gluconate and H2O2. We have compared the glucose levels obtained by these two methods in control Wistar rats, streptozotocin diabetic Wistar rats, Zucker fa/fa fatty rats and Zucker Diabetic Fatty rats. We found that the manual glucose assay and the glucose analyzer produced comparable values up to concentrations of about 25 mM. Above this level, samples should be diluted.
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PMID:Comparison of the glucose oxidase method for glucose determination by manual assay and automated analyzer. 1139 33


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