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

Oxidative stress is believed to be involved in the pathophysiology of a number of chronic diseases including atherosclerosis, diabetes, and cataracts and to accelerate the aging process. The aim of this study was to elucidate the role of various dietary fats in the in vivo modulation of CCl(4) induced oxidative stress using rat as a model. Rats were raised on diets enriched with saturated (Beef Tallow), n-9 (Sunola oil), n-6 (Safflower oil) or n-3 (Flaxseed oil) fatty acids and exposed to elevated oxidative stress by administration of CCl(4.) Plasma concentration of 8-iso-PGF(2alpha), antioxidant micronutrients and antioxidant enzymes were measured to examine changes to oxidative stress subsequent to the administration of CCl(4). The fatty acid profiles of plasma and RBC membranes reflected the fats fed in the different diets. CCl(4) administration had no significant effect on fatty acid composition of plasma or RBC lipids. Plasma 8-iso-PGF(2alpha) concentrations were elevated by CCl(4) administration regardless of the dietary fat fed. Within the induced oxidative groups the 8-iso-PGF(2alpha) concentrations were highest in Safflower oil followed by Sunola oil, Tallow and finally Flaxseed oil. Induction of oxidative stress by CCl(4) administration was associated with a significant reduction in Vitamin A content reaching a significantly lower concentration (P <0.05) in the Tallow and Flaxseed oil groups. Vitamin E concentrations were significantly lower (p = 0.01) in the Safflower oil and the Flaxseed oil than in the Tallow diet group following CCl(4) administration. Superoxide Dismutase (SOD) and Glutathione Peroxidase (GSHPx) activities were not affected by dietary fat manipulation. The results of this study indicate that dietary fat can modulate lipid peroxidation and antioxidant defenses when exposed to a pro-oxidant challenge.
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PMID:Modulation of carbon tetrachloride-induced oxidative stress by dietary fat in rats(open star). 1183 24

Oxidative stress plays an important role in the chronic complications of insulin-dependent diabetes mellitus (IDDM). Hyperketonemia, as well as hyperglycemia, is involved in the generation of oxygen-free radicals. We have studied the degree of oxidative stress in six patients before, during, and after correction of diabetic ketoacidosis (DKA) by determining the plasma ratios of C20 and C18 fatty acids to C16 fatty acids in the cholesteryl esters of the lipoproteins as well as in the plasma concentrations of the antioxidant vitamins A, C, and E. Lipid peroxidation was slightly increased prior to treatment. However, the C20/C16 ratio at 120 h was significantly decreased in comparison to the ratio at pretreatment (P<.025), at 6-8 h (P<.005), and at 24 h (P<.025). The C18/16 ratio at 120 h was also decreased in comparison to the ratio at 6-8 h (P<.025), indicating an increase in lipid peroxidation after correction of DKA. Vitamin A was below normal at pretreatment and was increased at 120 h (P<.05). Vitamin C was normal at pretreatment and decreased to low normal at 24 h (P<.005). Vitamin E was normal at pretreatment and decreased to below normal at 24 and 120 h, although the changes were not statistically significant. These data demonstrate that there is an increase in lipid peroxidation after the correction of DKA and therefore support the position that administering antioxidant vitamins during the treatment of DKA could be beneficial in minimizing oxidative stress and possibly both the acute and chronic complications of IDDM.
J Diabetes Complications
PMID:Lipid peroxidation and antioxidant vitamins prior to, during, and after correction of diabetic ketoacidosis. 1212 88

The BHE/Cdb rat has a maternally inherited mutation in the ATPase 6 mitochondrial gene that associates with impaired oxidative phosphorylation (OXPHOS) and glucose intolerance. A longevity study revealed that feeding an egg-rich (vitamin A-rich) diet delayed the onset of impaired glucose tolerance. Two experiments were conducted to test the hypothesis that BHE/Cdb rats require more dietary vitamin A than normal rats. Experiment 1 was a dose-response study examining OXPHOS in BHE/Cdb rats fed one of six levels of vitamin A. In experiment 2 BHE/Cdb and Sprague-Dawley rats were used. The rats were depleted of retinol stores, then repleted with 4 or 12 IU vitamin A/g diet. Vitamin A status was assessed in depleted, never depleted, and depleted/repleted rats. OXPHOS was optimized at 4 IU/g diet for the Sprague-Dawley rats and 12 IU/g diet for the BHE/Cdb rats. These results suggested that the criteria for vitamin intake adequacy in the BHE/Cdb rats is the optimization of mitochondrial OXPHOS. Using this criteria, we conclude that diabetes-prone BHE/Cdb rats require more dietary vitamin A than normal rats.
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PMID:Nutrient-gene interactions in mitochondrial function: vitamin A needs are increased in BHE/Cdb rats. 1262 67

Oxidative stress may play a role in the pathophysiology of diabetes and cardiovascular disease, but little is known about antioxidant status among individuals with the metabolic syndrome who are at high risk for developing these conditions. Using data from the Third National Health and Nutrition Examination Survey (1988-1994), we compared circulating concentrations of vitamins A, C, and E; retinyl esters; five carotenoids; and selenium in 8,808 U.S. adults aged > or = 20 years with and without the metabolic syndrome. After adjusting for age, sex, race or ethnicity, education, smoking status, cotinine concentration, physical activity, fruit and vegetable intake, and vitamin or mineral use, participants with the metabolic syndrome had significantly lower concentrations of retinyl esters, vitamin C, and carotenoids, except lycopene. With additional adjustment for serum lipid concentrations, vitamin E concentrations were significantly lower in participants with the metabolic syndrome than those without the syndrome. Retinol concentrations were similar between the two groups. After excluding participants with diabetes, the results were very similar. Consumption of fruits and vegetables was also lower among people with the metabolic syndrome. Adults with the metabolic syndrome have suboptimal concentrations of several antioxidants, which may partially explain their increased risk for diabetes and cardiovascular disease.
Diabetes 2003 Sep
PMID:The metabolic syndrome and antioxidant concentrations: findings from the Third National Health and Nutrition Examination Survey. 1294 75

Hyperinduced oxidant stress may have a role in the pathogenesis of diabetes and its micro- and macrovascular complications. Attaining euglycemia and the use of antioxidant vitamins could reduce oxidant stress and complications. In general, evidence does not support the use of supplements, and supplements are not recommended unless patients are deficient. Use of vitamins in excess may have adverse effects. Vitamin supplements are indicated in patients deficient in vitamins due to inadequate dietary intake or intestinal disease. Treatment with proper amounts of vitamins and antioxidants is best accomplished with a balanced diet including 3 servings of vegetables and 2 servings of fruits. Regarding supplementation of specific vitamins: carotene cannot be recommended in view of the possible harm and lack of benefit in clinical studies. Vitamin A (retinol) and Vitamin D should be repleted if deficient by laboratory assay. Excesses should be avoided. Vitamin A supplements, particularly in pregnancy, should not exceed 10,000 IU daily or a supplement should not exceed 25,000 units weekly. Vitamin E (alpha-tocopherol) alone in doses of 400 units is of questionable value, and larger doses may cause intracranial hemorrhage or interact negatively with lipid-lowering drugs. Vitamin E should not be used in patients who have bleeding disorders or patients on anticoagulants or acetylsalicylic acid (ASA). Vitamin C (ascorbic acid) losses in urine may be excessive in diabetic patients and may require repletion to 200 mg in nonsmokers and 250 mg in smokers. Further studies are needed testing: (1) vitamin supplementation in subgroups of patients at high risk for specific complications using tissue-specific indicators of oxidative stress; (2) the role of oxidative stress in nephropathy, diabetic myocardiopathy, dermopathy, joint limitation syndromes, peripheral edema, metabolic bone disease, and pregnancy; (3) the impact of renal failure on oxidative stress; and (4) the effects of diabetes and dietary vitamins on the relative amounts of retinoids, carotenoids, and vitamin E in the chylomicron and lipoproteins, and how this affects assimilation, oxidation of lipids, and atherosclerotic plaque formation.
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PMID:Advances in diabetes for the millennium: vitamins and oxidant stress in diabetes and its complications. 1564 9

Vitamin A (retinoid) is required in the adult brain to enable cognition, learning, and memory. While brain levels of retinoid diminish over the course of normal ageing, retinoid deficit is greater in late onset Alzheimer disease (LOAD) brains than in normal-aged controls. This paper reviews recent evidence supporting these statements and further suggests that genes necessary for the synthesis, transport and function of retinoid to and within the ageing brain are appropriate targets for treatment of LOAD. These genes tend to be clustered with genes that have been proposed as candidates in LOAD, are found at chromosomal regions linked to LOAD, and suggest the possibility of an overall coordinated regulation. This phenomenon is termed Chromeron and is analogous to the operon mechanism observed in prokaryotes. Suggested treatment targets are the retinoic-acid inactivating enzymes (CYP26)s, the retinol binding and transport proteins, retinol-binding protein (RBP)4 and transthyretin (TTR), and the retinoid receptors. TTR as a LOAD target is the subject of active investigation. The retinoid receptors and the retinoid-inactivating enzymes have previously been proposed as targets. This is the first report to suggest that RBP4 is an amenable treatment target in LOAD. RBP4 is elevated in type-2 diabetes and obesity, conditions associated with increased risk for LOAD. Fenretinide, a novel synthetic retinoic acid (RA) analog lowers RBP4 in glucose intolerant obese mice. The feasibility of using fenretinide either as an adjunct to present LOAD therapies, or on its own as an early prevention strategy should be determined.
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PMID:Retinoid receptors, transporters, and metabolizers as therapeutic targets in late onset Alzheimer disease. 1700 93

Retinol binding protein 4 (RBP4) is a protein secreted by adipocytes, and closely associated with insulin resistance. Whereas RBP4 is also mainly expressed in hepatocytes as the principal transport protein for retinol (vitamin A) in the circulation, and its pathophysiological role in liver remain unclear. The aim of this paper was to investigate the association between RBP4 and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Serum RBP4 and adiponectin concentrations were measured by radioimmunoassay in 52 diabetic patients who had NAFLD and 50 sex- and age-matched diabetic patients without any clinical features of liver diseases who had normal liver ultrasonic appearance and normal liver function. Serum RBP4 levels were elevated in diabetic patients with NAFLD (32.0+/-8.9 microg/ml vs. 41.3+/-9.8 microg/ml, p<0.001), while adiponectin decreased (17.4+/-9.3 microg/ml vs. 13.8+/-7.0 microg/ml, p=0.032). Male diabetic patients had higher serum RBP4 concentration and lower serum adiponectin concentration than female diabetic patients (38.5+/-9.9 microg/ml vs. 34.0+/-10.7 microg/ml, p=0.031 and 12.7+/-5.7 microg/ml vs. 20.23+/-9.8 microg/ml, p<0.001, respectively). Multiple logistic regression analysis revealed RBP4 and triglyceride as independent association factors for NAFLD, while the association between serum adiponectin and NAFLD was not significant. Increasing concentrations of RBP4 were independently and significantly associated with NAFLD in diabetic patients. In multiple linear regression analysis, alanine aminotransferase, fasting serum insulin and adiponectin were independent factors for serum RBP4 level. The study demonstrates that retinol binding protein 4 might contribute to the pathogenesis of nonalcoholic fatty liver disease.
Diabetes Res Clin Pract 2008 Feb
PMID:Serum retinol binding protein 4 and nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. 1790 83

Metabolic homeostasis in metazoans is regulated by endocrine control of insulin/IGF signaling (IIS) activity. Stress and inflammatory signaling pathways--such as Jun-N-terminal Kinase (JNK) signaling--repress IIS, curtailing anabolic processes to promote stress tolerance and extend lifespan. While this interaction constitutes an adaptive response that allows managing energy resources under stress conditions, excessive JNK activity in adipose tissue of vertebrates has been found to cause insulin resistance, promoting type II diabetes. Thus, the interaction between JNK and IIS has to be tightly regulated to ensure proper metabolic adaptation to environmental challenges. Here, we identify a new regulatory mechanism by which JNK influences metabolism systemically. We show that JNK signaling is required for metabolic homeostasis in flies and that this function is mediated by the Drosophila Lipocalin family member Neural Lazarillo (NLaz), a homologue of vertebrate Apolipoprotein D (ApoD) and Retinol Binding Protein 4 (RBP4). Lipocalins are emerging as central regulators of peripheral insulin sensitivity and have been implicated in metabolic diseases. NLaz is transcriptionally regulated by JNK signaling and is required for JNK-mediated stress and starvation tolerance. Loss of NLaz function reduces stress resistance and lifespan, while its over-expression represses growth, promotes stress tolerance and extends lifespan--phenotypes that are consistent with reduced IIS activity. Accordingly, we find that NLaz represses IIS activity in larvae and adult flies. Our results show that JNK-NLaz signaling antagonizes IIS and is critical for metabolic adaptation of the organism to environmental challenges. The JNK pathway and Lipocalins are structurally and functionally conserved, suggesting that similar interactions represent an evolutionarily conserved system for the control of metabolic homeostasis.
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PMID:Control of metabolic homeostasis by stress signaling is mediated by the lipocalin NLaz. 1939 Jun 10

Retinol-binding protein-4 (RBP4) is an emerging candidate drug target for type 2 diabetes and lipofuscin-mediated macular degeneration. The retinoic acid derivative fenretinide (N-(4-hydroxyphenyl) retinamide; HPR) exerts therapeutic effects in mouse models of obesity, diabetes, and Stargardt's disease by targeting RBP4. Fenretinide competes with retinoids for RBP4 binding, disrupts RBP4-transthyretin (TTR) complexes, and results in urinary secretion of RBP4 and systemic depletion of retinol. To enable the search for nonretinoid molecules with fenretinide-like activities we developed a HTS-compatible homogeneous TR-FRET assay monitoring the displacement of retinoic acid derivatives from RBP4 in high-density 384-well and 1536-well microtiter plate formats. The retinoid displacement assay proved to be highly sensitive and robust after miniaturization with IC(50)s for fenretinide and retinol ranging around 50 and 100 nM, respectively, and Z'-factors around 0.7. In addition, a surface plasmon resonance (SPR)-based secondary assay was developed to interrogate small molecule RBP4 binders for their ability to modulate the RBP4-TTR interaction. Finally, a 1.6 x 10(6) compound library was screened against the retinoid displacement assay. Several potent retinoid competitors were identified that also appeared to disrupt RBP4-TTR complexes. Some of these compounds could potentially serve as valuable tools to further probe RBP4 biology in the future.
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PMID:Time-resolved fluorescence resonance energy transfer and surface plasmon resonance-based assays for retinoid and transthyretin binding to retinol-binding protein 4. 1948 4

The aim of this study is to compare the effects of candesartan and olmesartan on insulin sensitivity-related parameters, before and after antihypertensive therapy. After a 4-week washout placebo period, 194 hypertensive (diastolic blood pressure (DBP) > or =80 mm Hg and systolic blood pressure (SBP) > or =130 mm Hg) patients with well-controlled type II diabetes were randomized to receive either 8 mg of candesartan once a day (o.d.) or 10 mg olmesartan o.d. and titrated after 1 month to 16 mg candesartan o.d. or 20 mg olmesartan o.d., respectively; the treatment period had a 1-year duration. We evaluated body weight, body mass index, SBP, DBP, glycated hemoglobin, fasting plasma glucose, M value, adiponectin (ADN), resistin (r), retinol-binding protein 4, visfatin, vaspin and high-sensitivity C-reactive protein (Hs-CRP) at their baseline values and after 6 and 12 months of treatment. We observed no variation in body weight or glycemic profile for either treatment. SBP and DBP were significantly reduced by both treatments (from 144+/-8/88+/-6 to 126+/-5/77+/-4 mm Hg by candesartan (P<0.001) and from 145+/-9/89+/-7 to 128+/-7/79+/-5 mm Hg by olmesartan (P<0.001)) without any difference between them. Retinol binding protein-4, r, and the vaspin value decreased in the candesartan group but not in olmesartan group. The M value, visfatin and ADN increased with candesartan, whereas no significant variations were observed with olmesartan. Both treatments resulted in a similar reduction in Hs-CRP. Although both therapies resulted in similar reductions in blood pressure, candesartan therapy was more effective than olmesartan therapy in improving insulin sensitivity.
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PMID:Differential effects of candesartan and olmesartan on adipose tissue activity biomarkers in type II diabetic hypertensive patients. 2055 29


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