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fenofibrate and diabetes

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https://www.readbyqxmd.com/read/28036029/fenofibrate-therapy-restores-antioxidant-protection-and-improves-myocardial-insulin-resistance-in-a-rat-model-of-metabolic-syndrome-and-myocardial-ischemia-the-role-of-angiotensin-ii
#1
Luz Ibarra-Lara, María Sánchez-Aguilar, Alicia Sánchez-Mendoza, Leonardo Del Valle-Mondragón, Elizabeth Soria-Castro, Elizabeth Carreón-Torres, Eulises Díaz-Díaz, Héctor Vázquez-Meza, Verónica Guarner-Lans, María Esther Rubio-Ruiz
Renin-angiotensin system (RAS) activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS) and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II)/Angiotensin II type 1 receptor (AT1) and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia...
December 28, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28030716/association-of-fenofibrate-therapy-with-long-term-cardiovascular-risk-in-statin-treated-patients-with-type-2-diabetes
#2
Marshall B Elam, Henry N Ginsberg, Laura C Lovato, Marshall Corson, Joseph Largay, Lawrence A Leiter, Carlos Lopez, Patrick J O'Connor, Mary Ellen Sweeney, Daniel Weiss, William T Friedewald, John B Buse, Hertzel C Gerstein, Jeffrey Probstfield, Richard Grimm, Faramarz Ismail-Beigi, David C Goff, Jerome L Fleg, Yves Rosenberg, Robert P Byington
Importance: Patients with type 2 diabetes are at high risk of cardiovascular disease (CVD) in part owing to hypertriglyceridemia and low high-density lipoprotein cholesterol. It is unknown whether adding triglyceride-lowering treatment to statin reduces this risk. Objective: To determine whether fenofibrate reduces CVD risk in statin-treated patients with type 2 diabetes. Design, Setting, and Participants: Extended posttrial follow-up of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Study participants between July 2009 and October 2014...
December 28, 2016: JAMA Cardiology
https://www.readbyqxmd.com/read/27996196/reverse-translational-study-of-fenofibrate-s-observed-effects-in-diabetes-associated-retinopathy
#3
R A Farris, E T Price
Clinical trials suggest that fenofibrate reduces the progression of retinopathies in patients with type 2 diabetes. Furthermore, patients with retinopathies have elevated levels of inflammatory chemokines and dysfunctional retinal angiogenesis. Therefore, we investigated the effects of fenofibrate on the production of inflammatory chemokines and genes associated with angiogenesis. Retinal pigment epithelial cells (RPECs) were cultured with IL-1β and fenofibrate ranging from 1-50 μM. ENA-78, IL-8, and RANTES were measured in cell culture by ELISA...
December 20, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27992863/effects-of-high-density-lipoprotein-raising-therapies-on-cardiovascular-outcomes-in-patients-with-type-2-diabetes-mellitus-with-or-without-renal-impairment-the-action-to-control-cardiovascular-risk-in-diabetes-study
#4
Vasilios Papademetriou, Laura Lovato, Costas Tsioufis, William Cushman, William B Applegate, Amy Mottle, Zubin Punthakee, Eric Nylen, Michael Doumas
BACKGROUND: The role of high density lipoprotein-raising interventions in addition to statin therapy in patients with diabetes remains controversial. Chronic kidney disease (CKD) is a strong modifier of cardiovascular (CV) outcomes. We therefore investigated the impact of CKD status at baseline on outcomes in patients with diabetes randomized to standard statin or statin plus fenofibrate treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial. METHODS: Among 5,464 participants in the ACCORD lipid trial, 3,554 (65%) were free of CKD at baseline, while 1,910 (35%) had mild to moderate CKD...
December 17, 2016: American Journal of Nephrology
https://www.readbyqxmd.com/read/27973425/zerumbone-a-bioactive-sesquiterpene-ameliorates-diabetes-induced-retinal-microvascular-damage-through-inhibition-of-phospho-p38-mitogen-activated-protein-kinase-and-nuclear-factor-%C3%AE%C2%BAb-pathways
#5
Wayne Young Liu, Thing-Fong Tzeng, I-Min Liu
Zerumbone ameliorates retinal damage by blocking advanced glycation end products and their receptor system in streptozotocin-diabetic rats. Because of the multiple factors involved in diabetic retinopathy (DR) etiology, the mechanisms of zerumbone that are mainly responsible for its ameliorative effect on DR need to be further clarified. In the present study, zerumbone (20 mg or 40 mg/kg) or fenofibric acid (100 mg/kg) was orally administered to diabetic rats by intragastric gavage once daily for three consecutive months...
December 11, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27889747/alisol-a-24-acetate-prevents-hepatic-steatosis-and-metabolic-disorders-in-hepg2-cells
#6
Lu Zeng, WaiJiao Tang, JinJin Yin, LiJuan Feng, Yabing Li, Xiaorui Yao, BenJie Zhou
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders including hepatic lipid accumulation and inflammation. Alisol A 24-acetate, a triterpene from Alismatis rhizome, has multiple biologic activities such as hypolipidemic, anti-inflammatory and anti-diabetic. Thus we hypothesized that Alisol A 24 -acetate would have effect on NAFLD. The present study was conducted to investigate the therapeutic effects and potential mechanisms of Alisol A 24-acetate against hepatic steatosis in a free fatty acids (FFAs) induced NAFLD cell model...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27868450/pharmacological-management-of-diabetic-dyslipidemia
#7
T D Filippatos, M Florentin, M Georgoula, M S Elisaf
Diabetes mellitus is associated with increased cardiovascular disease (CVD) risk. Areas covered: Main goal of hypolipidemic treatment in diabetic patients is low-density lipoprotein cholesterol (LDL-C) lowering with the use of statins. Addition of ezetimibe is useful in diabetic patients who cannot achieve their LDL-C target. However, many diabetic patients have increased residual CVD risk, which is mainly attributed to high triglycerides and low high-density lipoprotein (HDL-C) values. The addition of fenofibrate targets these variables and possibly reduces residual CVD risk, but a possible beneficial effect has been shown only in a pre-specified subgroup analysis in patients with high triglycerides and low HDL-C values...
December 2, 2016: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27720395/fenofibrate-inhibits-cytochrome-p450-epoxygenase-2c-activity-to-suppress-pathological-ocular-angiogenesis
#8
Yan Gong, Zhuo Shao, Zhongjie Fu, Matthew L Edin, Ye Sun, Raffael G Liegl, Zhongxiao Wang, Chi-Hsiu Liu, Samuel B Burnim, Steven S Meng, Fred B Lih, John Paul SanGiovanni, Darryl C Zeldin, Ann Hellström, Lois E H Smith
Neovascular eye diseases including retinopathy of prematurity, diabetic retinopathy and age-related-macular-degeneration are major causes of blindness. Fenofibrate treatment in type 2 diabetes patients reduces progression of diabetic retinopathy independent of its peroxisome proliferator-activated receptor (PPAR)α agonist lipid lowering effect. The mechanism is unknown. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP)2C with higher affinity than to PPARα. CYP2C metabolizes ω-3 long-chain polyunsaturated fatty acids (LCPUFAs)...
November 2016: EBioMedicine
https://www.readbyqxmd.com/read/27702549/thioredoxin-interacting-protein-mediates-lipid-induced-impairment-of-glucose-uptake-in-skeletal-muscle
#9
Ashok Mandala, Nabanita Das, Sudarshan Bhattacharjee, Bidisha Mukherjee, Satinath Mukhopadhyay, Sib Sankar Roy
Insulin resistance (IR) is an important determinant of type-2 diabetes mellitus (T2DM). Free fatty acids (FFAs) induce IR by various mechanisms. A surfeit of circulating FFA leads to intra-myocellular lipid accumulation that induces mitochondrial ROS generation and worsens IR. However, the molecular mechanisms behind are unclear. We identified thioredoxin interacting protein (TxNIP), which is overexpressed in T2DM, to be a promoter of ROS-induced IR. We observed upregulation of TxNIP upon palmitate treatment in skeletal muscle cells that led to ROS generation and Glut-4 downregulation resulting in impaired glucose-uptake...
October 28, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27700224/evidence-based-treatment-of-diabetic-retinopathy
#10
Hala El Rami, Rasha Barham, Jennifer K Sun, Paolo S Silva
Diabetic retinopathy (DR) is the most frequent microvascular complication from diabetes and requires annual screening and at least annual follow-up. A systemic approach to optimize blood glucose and blood pressure may halt progression to severe stages of DR and obviate the need for ocular treatment. Although there is evidence of benefit from fenofibrate or intravitreous antiVEGF treatment for eyes with nonproliferative DR (NPDR), these therapies are not standard care for NPDR at this time. Some patients with severe NPDR, especially those with type 2 diabetes, benefit from early panretinal photocoagulation (PRP)...
2017: Seminars in Ophthalmology
https://www.readbyqxmd.com/read/27662905/fenofibrate-decreases-insulin-clearance-and-insulin-secretion-to-maintain-insulin-sensitivity
#11
Sadeesh K Ramakrishnan, Lucia Russo, Simona S Ghanem, Payal R Patel, Ana Maria Oyarce, Garrett Heinrich, Sonia M Najjar
High fat diet reduces the expression of CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1), a transmembrane glycoprotein that promotes insulin clearance and down-regulates fatty acid synthase activity in the liver upon its phosphorylation by the insulin receptor. Because peroxisome proliferator-activated receptor α (PPARα) transcriptionally suppresses CEACAM1 expression, we herein examined whether high fat down-regulates CEACAM1 expression in a PPARα-dependent mechanism. By activating PPARα, the lipid-lowering drug fenofibrate reverses dyslipidemia and improves insulin sensitivity in type 2 diabetes in part by promoting fatty acid oxidation...
November 11, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27627093/-a-near-future-of-treatment-of-dyslipidemia-in-type-2%C3%A2-diabetics
#12
Michal Vrablík
UNLABELLED: Dyslipidemia in type 2 diabetics represents a complex change of lipoprotein metabolism that is highly proatherogenic. It originates on a genetic background in the context of insulin resistance and affects lipoprotein metabolism at multiple levels (e.g. hepatocyte, enterocyte, intravascular processing) mainly in the postprandial phase. The treatment of diabetic (atherogenic) dyslipidemia is an effective option to lower the risk of both macro- and microvascular complications of diabetes...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27609708/-fibrates-therapy-rational-use-fenofibrate-2016-executive-summary
#13
Angel Brea, Jesús Millán, Juan F Ascaso, Mariano Blasco, Angel Díaz, Pedro González-Santos, Antonio Hernández-Mijares, Teresa Mantilla, Juan C Pedro-Botet, Xavier Pintó
To control lipid factors risk, beyond proper management of LDL cholesterol according to individual risk, detection and treatment of atherogenic dyslipidemia and abnormal levels of triglycerides or HDL cholesterol it should be considered for address a global cardiovascular protection, both in primary and secondary prevention. In this sense, these recommendations collect data on efficacy and safety about the combination statin with fibrates, often necessary for total control of dyslipidemia, particularly in patients with metabolic disorders such as diabetes mellitus, metabolic syndrome or visceral obesity...
November 2016: Clínica e Investigación en Arteriosclerosis
https://www.readbyqxmd.com/read/27568833/mechanistic-insight-of-diabetic-nephropathy-and-its-pharmacotherapeutic-targets-an-update
#14
REVIEW
Niloy Bhattacharjee, Sujata Barma, Nandita Konwar, Saikat Dewanjee, Prasenjit Manna
Diabetic nephropathy (DN), a chronic complication of diabetes, is charecterized by glomerular hypertrophy, proteinuria, decreased glomerular filtration, and renal fibrosis resulting in the loss of renal function. Although the exact cause of DN remains unclear, several mechanisms have been postulated, such as hyperglycemia-induced renal hyper filtration and renal injury, AGEs-induced increased oxidative stress, activated PKC-induced increased production of cytokines, chemokines, and different inflammatory and apoptotic signals...
November 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27562996/-the-effect-of-fenofibrate-on-expression-of-genes-involved-in-fatty-acids-beta-oxidation-and-associated-free-radical-processes
#15
A P Gureev, M L Shmatkova, V Yu Bashmakov, A A Starkov, V N Popov
Fenofibrate is a synthetic ligand for peroxisome proliferator-activated receptors subtype alpha (PPARa); it is used for the treatment of a wide range of metabolic diseases such as hypertriglyceridemia, dyslipidemia, diabetes and various neurodegenerative diseases. We have studied the effect of fenofibrate on b-oxidation of fatty acids and related free-radical processes. The most effective concentration of fenofibrate (0.3%) added to the chow caused a significant decrease of the body weight of mice. The data obtained by quantitative PCR demonstrated increased hepatic gene expression responsible for b-oxidation of fatty acids in peroxisomes and mitochondria...
May 2016: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/27543085/interaction-of-ppar%C3%AE-with-the-canonic-wnt-pathway-in-the-regulation-of-renal-fibrosis
#16
Rui Cheng, Lexi Ding, Xuemin He, Yusuke Takahashi, Jian-Xing Ma
Peroxisome proliferator-activated receptor-α (PPARα) displays renoprotective effects with an unclear mechanism. Aberrant activation of the canonical Wnt pathway plays a key role in renal fibrosis. Renal levels of PPARα were downregulated in both type 1 and type 2 diabetes models. The PPARα agonist fenofibrate and overexpression of PPARα both attenuated the expression of fibrotic factors, and suppressed high glucose-induced or Wnt3a-induced Wnt signaling in renal cells. Fenofibrate inhibited Wnt signaling in the kidney of diabetic rats...
December 2016: Diabetes
https://www.readbyqxmd.com/read/27525681/fenofibrate-and-diabetic-retinopathy
#17
REVIEW
Jared E Knickelbein, Akshar B Abbott, Emily Y Chew
Diabetic retinopathy, a common and sight-threatening microvascular complication of diabetes mellitus, is a leading cause of blindness among working-aged adults. Medical therapies including intensive control of hyperglycemia and hypertension have been shown to reduce the incidence and progression of diabetic retinopathy. The association of dyslipidemia and treatment with statins with diabetic retinopathy is inconsistent in epidemiologic studies. However, two recent randomized clinical trials have demonstrated beneficial effects of systemic fenofibrate therapy in reducing the progression of diabetic retinopathy independently of serum lipid levels...
October 2016: Current Diabetes Reports
https://www.readbyqxmd.com/read/27479624/vision-loss-in-older-adults
#18
Allen L Pelletier, Ledy Rojas-Roldan, Janis Coffin
Vision loss affects 37 million Americans older than 50 years and one in four who are older than 80 years. The U.S. Preventive Services Task Force concludes that current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in adults older than 65 years. However, family physicians play a critical role in identifying persons who are at risk of vision loss, counseling patients, and referring patients for disease-specific treatment. The conditions that cause most cases of vision loss in older patients are age-related macular degeneration, glaucoma, ocular complications of diabetes mellitus, and age-related cataracts...
August 1, 2016: American Family Physician
https://www.readbyqxmd.com/read/27334889/therapeutic-targeting-of-diabetic-retinal-neuropathy-as-a-strategy-in-preventing-diabetic-retinopathy
#19
REVIEW
Gabriela de Moraes, Christopher J Layton
Diabetes causes a panretinal neurodegeneration herein termed diabetic retinal neuropathy, which manifests in the retina early and progresses throughout the disease. Clinical manifestations include changes in the ERG, perimetry, dark adaptation, contrast sensitivity and colour vision which correlate with laboratory findings of thinning of the retinal neuronal layers, increased apoptosis in neurons and activation of glial cells. Possible mechanisms include oxidative stress, neuronal AGE accumulation, altered balance of neurotrophic factors and loss of mitohormesis...
December 2016: Clinical & Experimental Ophthalmology
https://www.readbyqxmd.com/read/27271603/dehydroeburicoic-acid-from-antrodia-camphorata-prevents-the-diabetic-and-dyslipidemic-state-via-modulation-of-glucose-transporter-4-peroxisome-proliferator-activated-receptor-%C3%AE-expression-and-amp-activated-protein-kinase-phosphorylation-in-high-fat-fed-mice
#20
Yueh-Hsiung Kuo, Cheng-Hsiu Lin, Chun-Ching Shih
This study investigated the potential effects of dehydroeburicoic acid (TT), a triterpenoid compound from Antrodia camphorata, in vitro and examined the effects and mechanisms of TT on glucose and lipid homeostasis in high-fat-diet (HFD)-fed mice. The in vitro study examined the effects of a MeOH crude extract (CruE) of A. camphorata and Antcin K (AnK; the main constituent of fruiting body of this mushroom) on membrane glucose transporter 4 (GLUT4) and phospho-Akt in C2C12 myoblasts cells. The in vitro study demonstrated that treatment with CruE, AnK and TT increased the membrane levels of glucose transporter 4 (GLUT4) and phospho-Akt at different concentrations...
June 3, 2016: International Journal of Molecular Sciences
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