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)

Increased oxidative stress in diabetes mellitus may underlie the development of endothelial cell dysfunction by decreasing the availability of nitric oxide (NO) as well as by activating pro-inflammatory pathways. In the arterial wall, redox imbalance and oxidation of tetrahydrobiopterin (BH4) uncouples endothelial nitric oxide synthase (eNOS). This results in decreased production and increased consumption of NO, and generation of free radicals, such as superoxide and peroxynitrite. In the mitochondria, increased redox potential uncouples oxidative phosphorylation, resulting in inhibition of electron transport and increased transfer of electrons to molecular oxygen to form superoxide and other oxidant radicals. Coenzyme Q10 (CoQ), a potent antioxidant and a critical intermediate of the electron transport chain, may improve endothelial dysfunction by 'recoupling' eNOS and mitochondrial oxidative phosphorylation. CoQ supplementation may also act synergistically with anti-atherogenic agents, such as fibrates and statins, to improve endotheliopathy in diabetes.
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PMID:Coenzyme Q10 and diabetic endotheliopathy: oxidative stress and the 'recoupling hypothesis'. 1525 11

During the development of the autoimmune disease, insulin-dependent diabetes mellitus (IDDM) islet cell death is thought to be mediated in part by oxygen and nitrogen free radicals and interleukin 1beta (IL-1beta), secreted by activated macrophages. Free radicals disrupt the homeostasis of biological systems by damaging major constituent molecules such as lipids, proteins, and DNA. Islet cells are quite susceptible to oxidative damage due to low levels of antioxidant enzymes involved in free radical consumption. If IDDM is associated with an imbalance of oxidative stresses and antioxidant responses in islet cells, then it may be possible to ameliorate disease by supplementating antioxidant defenses. In this study, the antioxidants coenzyme Q10 and lipoic acid were able to block IL-1beta-mediated inhibition of glucose-stimulated insulin secretion from islet cells at 10(-12) M and 10(-9) M, respectively.
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PMID:Effects of antioxidants coenzyme Q10 and lipoic acid on interleukin-1 beta-mediated inhibition of glucose-stimulated insulin release from cultured mouse pancreatic islets. 1580 64

The heart is one of the organs affected during the later stages of diabetes. Mitochondrial function has already been proposed to be affected during the course of diabetes. Nevertheless, little information is known concerning the impact of antioxidants in heart mitochondria of a milder model for diabetes, such as the Goto-Kakizaki (GK) rat, where mitochondrial function appears ameliorated. The objective of this work was to test if injections of Vitamin E and Coenzyme Q10, alone and in combination, were able to modify mitochondrial performance in the hearts of GK rats. Several aspects of mitochondrial function were measured, such as the respiratory control ratio and the electric potential, as well as the mitochondrial accumulation of Vitamin E and Coenzymes Q9 and Q10. We observed that only Vitamin E appeared to have a positive impact on the mitochondrial phosphorylation efficiency and on mitochondrial performance, namely on the ability to generate the electric transmembrane potential in the presence of supra-physiological calcium concentrations. Vitamin E administration also increased the mitochondrial concentration of Coenzyme Q10. None of the treatments was able to reverse the diabetic phenotype in GK rats. We conclude that in this model of mild hyperglycemia, administration of antioxidants may have a marginal positive impact on mitochondrial function.
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PMID:Vitamin E or coenzyme Q10 administration is not fully advantageous for heart mitochondrial function in diabetic goto kakizaki rats. 1612 Mar 65

Using brain mitochondria isolated from 20-month-old diabetic Goto-Kakizaki rats, we evaluated the efficacy of CoQ10 treatment against mitochondrial dysfunction induced by Abeta1-40. For that purpose, several mitochondrial parameters were evaluated: respiratory indexes (RCR and ADP/O ratio), transmembrane potential (DeltaPsim), repolarization lag phase, repolarization and ATP levels and the capacity of mitochondria to produce hydrogen peroxide. We observed that 4 microM Abeta1-40 induced a significant decrease in the RCR and ATP content and a significant increase in hydrogen peroxide production. CoQ10 treatment attenuated the decrease in oxidative phosphorylation efficiency and avoided the increase in hydrogen peroxide production induced by the neurotoxic peptide. These results indicate that CoQ10 treatment counteracts brain mitochondrial alterations induced by Abeta1-40 suggesting that CoQ10 therapy can help to avoid a drastic energy deficiency that characterizes diabetes and Alzheimer's disease pathophysiology.
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PMID:CoQ10 therapy attenuates amyloid beta-peptide toxicity in brain mitochondria isolated from aged diabetic rats. 1612 99

Coenzyme Q10 is a vitamin-like substance used in the treatment of a variety of disorders primarily related to suboptimal cellular energy metabolism and oxidative injury. Studies supporting the efficacy of coenzyme Q10 appear most promising for neurodegenerative disorders such as Parkinson's disease and certain encephalomyopathies for which coenzyme Q10 has gained orphan drug status. Results in other areas of research, induding treatment of congestive heart failure and diabetes, appear to be contradictory or need further clarification before proceeding with recommendations. Coenzyme Q10 appears to be a safe supplement with minimal side effects and low drug interaction potential.
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PMID:Coenzyme Q10. 1619 May 4

Maternally-inherited diabetes and deafness (MIDD) has been related to an A to G transition in the mitochondrial tRNA Leu (UUR) gene at the base pair 3243. Although some previous articles have reported that this mutation may be a cause of cardiomyopathy in diabetes, the degree of cardiac involvement and a specific treatment has not been established. Here, we reported a case of a patient with MIDD who developed congestive heart failure and the therapeutic usefulness of Coenzyme Q10 (CoQ10). In our patient, after the introduction of Coenzyme Q10 150 mg/day, there was a gradual improvement on left ventricular function evaluated by echocardiography. The fractional shortening (FS) and ejection fraction (EF) increased from 26 to 34% and from 49 to 64%, respectively. No side effects were noted. Three months after CoQ10 discontinuation, the parameters of systolic function evaluated by echocardiography decreased, suggesting that CoQ10 had a beneficial effect. Identification of diabetes and cardiomyopathy due to mitochondrial gene mutation may have therapeutic implications and Coenzyme Q10 is a possible adjunctive treatment in such patients.
Diabetes Res Clin Pract 2006 Apr
PMID:Myocardial dysfunction in mitochondrial diabetes treated with Coenzyme Q10. 1625 79

Although coenzyme Q10 (CoQ10) is a component of the oxidative phosphorylation process in mitochondria that converts the energy in carbohydrates and fatty acids into ATP to drive cellular machinery and synthesis, its effect in type I diabetes is not clear. We have studied the effect of 4 wk of treatment with CoQ10 (10 mg/kg, ip, daily) in streptozotocin (STZ)-induced (40 mg/kg, iv in adult rats) type I diabetes rat models. Treatment with CoQ10 produced a significant decrease in elevated levels of glucose, cholesterol, triglycerides, very-low-density lipoprotein, low-density lipoprotein, and atherogenic index and increased high-density lipoprotein cholesterol levels in diabetic rats. CoQ10 treatment significantly decreased the area under the curve over 120 min for glucose in diabetic rats, without affecting serum insulin levels and the area under the curve over 120 min for insulin in diabetic rats. CoQ10 treatment also reduced lipid peroxidation and increased antioxidant parameters like superoxide dismutase, catalase, and glutathione in the liver homogenates of diabetic rats. CoQ10 also lowered the elevated blood pressure in diabetic rats. In conclusion, CoQ10 treatment significantly improved deranged carbohydrate and lipid metabolism of experimental chemically induced diabetes in rats. The mechanism of its beneficial effect appears to be its antioxidant property.
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PMID:Effect of coenzyme Q10 on catalase activity and other antioxidant parameters in streptozotocin-induced diabetic rats. 1638

Antioxidants are emerging as prophylactic and therapeutic agents. These are the agents, which scavenge free radicals otherwise reactive oxygen species and prevent the damage caused by them. Free radicals have been associated with pathogenesis of various disorders like cancer, diabetes, cardiovascular diseases, autoimmune diseases, neurodegenerative disorders and are implicated in aging. Several antioxidants like SOD, CAT, epigallocatechin-3-O-gallate, lycopene, ellagic acid, coenzyme Q10, indole-3-carbinol, genistein, quercetin, vitamin C and vitamin E have been found to be pharmacologically active as prophylactic and therapeutic agents for above mentioned diseases. Antioxidants are part of diet but their bioavailability through dietary supplementation depends on several factors. This major drawback of dietary agents may be due to one or many of the several factors like poor solubility, inefficient permeability, instability due to storage of food, first pass effect and GI degradation. Conventional dosage forms may not result in efficient formulation owing to their poor biopharmaceutical properties. Principles of novel drug delivery systems need to be applied to significantly improve the performance of antioxidants. Novel drug delivery systems (NDDS) would also help in delivery of these antioxidants by oral route, as this route is of prime importance when antioxidants are intended for prophylactic purpose. Implication of NDDS for the delivery of antioxidants is largely governed by physicochemical characteristics, biopharmaceutical properties and pharmacokinetic parameters of the antioxidant to be formulated. Recently, chemical modifications, coupling agents, liposomes, microparticles, nanoparticles and gel-based systems have been explored for the delivery of these difficult to deliver molecules. Results from several studies conducted across the globe are positive and provided us with new anticipation for the improvement of human healthcare.
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PMID:Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective. 1679 Feb 90

The study seeks to describe the use of dietary supplements promoted for cardiovascular health and the relation between supplement use and coronary artery disease (CAD) and the presence of major CAD risk factors. The aim is also to explore whether use of medications for the treatment of cardiovascular disease or diabetes mellitus (DM) is associated with supplement use. We performed a cross-sectional analysis of the 1999 to 2002 National Health and Nutrition Examination Survey (NHANES) of 6,671 adults (representing 119.3 million US adults) aged > or =40 years. We categorized adults into 4 nonoverlapping groups as (1) having reported CAD or stroke (CAD/stroke), (2) DM without CAD/stroke, (3) hypertension (HTN) or hypercholesterolemia (HC) without CAD/stroke or DM (HTN/HC), or (4) none of these conditions (no reported CAD/CAD risk) and performed weighted (NHANES) multiple logistic regression to determine the odds of using supplements (reference group, no reported CAD/CAD risk). After controlling for sociodemographics, health, and lifestyle factors, we found that persons with CAD/Stroke used more supplements (any), vitamin E, folic acid, and niacin, and less fish oil. Those with DM used less coenzyme Q10, and adults with HTN/HC used more supplements (any), herbs (any), and ginseng. Adults with CAD/stroke who used medications for the treatment of cardiovascular disease or DM were more likely to use folic acid compared with those who did not use medications for these conditions. In adults with CAD/stroke, DM, or HTN/HC, those who did not use medications for these conditions were more likely to use herbs and other select supplements. In conclusion, use of dietary supplements is common in those with CAD or CAD risks.
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PMID:Use of dietary supplements among United States adults with coronary artery disease and atherosclerotic risks. 1731 68

Hyperglycemia-induced oxidative stress plays a crucial role in the pathogenesis of vascular complications in diabetes. Although some clinical evidences suggest the use of an antioxidant reagent coenzyme Q10 in diabetes with hypertension, the direct effect of coenzyme Q10 on the endothelial functions has not been examined. In the present study, we therefore investigated the protective effect of coenzyme Q10 against high glucose-induced oxidative stress in human umbilical vein endothelial cells (HUVEC). HUVEC exposed to high glucose (30 mM) exhibited abnormal properties, including the morphological and biochemical features of apoptosis, overproduction of reactive oxygen species, activation of protein kinase Cbeta2, and increase in endothelial nitric oxide synthase expression. Treatment with coenzyme Q10 strongly inhibited these changes in HUVEC under high glucose condition. In addition, coenzyme Q10 inhibited high glucose-induced cleavage of poly(ADP-ribose) polymerase, an endogenous caspase-3 substrate. These results suggest that coenzyme Q10 prevents reactive oxygen species-induced apoptosis through inhibition of the mitochondria-dependent caspase-3 pathway. Moreover, consistent with previous reports, high glucose caused upregulation of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in HUVEC, and promoted the adhesion of U937 monocytic cells. Coenzyme Q10 displayed potent inhibitory effects against these endothelial abnormalities. Thus, we provide the first evidence that coenzyme Q10 has a beneficial effect in protecting against the endothelial dysfunction by high glucose-induced oxidative stress in vitro.
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PMID:Coenzyme Q10 prevents high glucose-induced oxidative stress in human umbilical vein endothelial cells. 1743 78


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