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fenofibrate and diabetes

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...
November 25, 2016: Cellular Physiology and Biochemistry
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
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)...
September 30, 2016: EBioMedicine
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
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)...
October 4, 2016: Seminars in Ophthalmology
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
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
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...
September 5, 2016: Clínica e Investigación en Arteriosclerosis
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...
August 25, 2016: European Journal of Pharmacology
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
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 down-regulated in both type 1 and type 2 diabetic models. The PPARα agonist fenofibrate and over-expression of PPARα both attenuated expression of fibrotic factors and suppressed high glucose- or Wnt3a-induced Wnt signaling in renal cells. Fenofibrate inhibited Wnt signaling in the kidney of diabetic rats...
August 19, 2016: Diabetes
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
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
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...
June 23, 2016: Clinical & Experimental Ophthalmology
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...
2016: International Journal of Molecular Sciences
Leszek Czupryniak, Shashank R Joshi, Jaideep A Gogtay, Meena Lopez
OBJECTIVE: Micronized fenofibrate prevents the progression of microvascular complications in type 2 diabetes, but no systematic review has summarized these effects. Therefore, we performed a systematic review to investigate the effects of micronized fenofibrate on type 2 diabetes-related microvascular complications. RESEARCH DESIGN AND METHODS: The PubMed database was systematically searched for trials in English language published between January 1990 and November 2015 that examined the effects of fenofibrate on microvascular complications in patients with type 2 diabetes...
August 2016: Expert Opinion on Pharmacotherapy
Yueh-Hsiung Kuo, Cheng-Hsiu Lin, Chun-Ching Shih, Chang-Syun Yang
The purpose of this study was to screen firstly the potential effects of antcin K (AnK), the main constituent of the fruiting body of Antrodia camphorata, in vitro and further evaluate the activities and mechanisms in high-fat-diet- (HFD-) induced mice. Following 8-week HFD-induction, mice were treated with AnK, fenofibrate (Feno), metformin (Metf), or vehicle for 4 weeks afterward. In C2C12 myotube cells, the membrane GLUT4 and phospho-Akt expressions were higher in insulin and AnK-treated groups than in the control group...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
Danjun Song, Zanbo Chu, Luo Min, Tan Zhen, Pengxu Li, Liyuan Han, Shizhong Bu, Julin yang, F J Gonzale, Aiming Liu
BACKGROUND: Concurrence of high glucose or diabetes in patients with dyslipidemia is presenting major challenges for clinicians. Although sporadically reported, a rational basis for the use of fibrates for the treatment of dyslipidemia with concurrent metabolic syndrome has not been established. METHODS: In this study, wild-type (WT) and Ppara-null (KO) mice were fed a serial gemfibrozil- and fenofibrate-containing diet under the same experimental conditions for 14 days...
April 2016: Die Pharmazie
Arijit Ghosh, Pranab Kumar Sahana, Chanchal Das, Ananya Mandal, Nilanjan Sengupta
INTRODUCTION: Diabetic dyslipidaemia poses a therapeutic challenge. New therapies have emerged in this patient subgroup to enhance outcome and improve compliance. AIM: The aim of this study was to compare the effectiveness and safety of add on therapy of saroglitazar and fenofibrate with metformin in Indian patients with diabetic dyslipidaemia. MATERIALS AND METHODS: Adults patients with diabetic dyslipidaemia fulfilling the inclusion criteria were randomized in two groups...
March 2016: Journal of Clinical and Diagnostic Research: JCDR
László Márk, Győző Dani
The incidence and the public health importance of diabetes mellitus are growing continuously. Despite the improvement observed in recent years, the leading cause of morbidity and mortality of diabetics are cardiovascular diseases. The diagnosis of diabetes mellitus constitutes such a high risk as the known presence of vascular disease. Diabetic dyslipidaemia is characterised by high fasting and postprandial triglyceride levels, low HDL level, and slightly elevated LDL-cholesterol with domination of atherogenic small dense LDL...
May 8, 2016: Orvosi Hetilap
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