scholarly journals Peroxisome Proliferator-Activated Receptors in Diabetic Nephropathy

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-11 ◽  
Author(s):  
Shinji Kume ◽  
Takashi Uzu ◽  
Keiji Isshiki ◽  
Daisuke Koya
Keyword(s):  
Diabetic Nephropathy ◽  
Therapeutic Potential ◽  
Experimental Studies ◽  
Renin Angiotensin System ◽  
Pressure Control ◽  
Peroxisome Proliferator ◽  
Patients With Diabetes ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
Stage Renal Disease

Diabetic nephropathy is a leading cause of end-stage renal disease, which is increasing in incidence worldwide, despite intensive treatment approaches such as glycemic and blood pressure control in patients with diabetes mellitus. New therapeutic strategies are needed to prevent the onset of diabetic nephropathy. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostases. These agents might prevent the progression of diabetic nephropathy, since PPAR agonists improve dyslipidemia and insulin resistance. Furthermore, data from murine models suggest that PPAR agonists also have independent renoprotective effects by suppressing inflammation, oxidative stress, lipotoxicity, and activation of the renin-angiotensin system. This review summarizes data from clinical and experimental studies regarding the relationship between PPARs and diabetic nephropathy. The therapeutic potential of PPAR agonists in the treatment of diabetic nephropathy is also discussed.

scholarly journals The Renoprotective Actions of Peroxisome Proliferator-Activated Receptors Agonists in Diabetes

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
M. C. Thomas ◽  
K. A. Jandeleit-Dahm ◽  
C. Tikellis
Keyword(s):  
Cardiovascular Effects ◽  
Lipid Lowering ◽  
Peroxisome Proliferator ◽  
Oral Hypoglycaemic Agents ◽  
Diabetic Kidney ◽  
Critical Pathways ◽  
Patients With Diabetes ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
In The Diabetic Kidney

Pharmaceutical agonists of peroxisome proliferator-activated receptors (PPARs) are widely used in the management of type 2 diabetes, chiefly as lipid-lowering agents and oral hypoglycaemic agents. Although most of the focus has been placed on their cardiovascular effects, both positive and negative, these agents also have significant renoprotective actions in the diabetic kidney. Over and above action on metabolic control and effects on blood pressure, PPAR agonists also appear to have independent effects on a number of critical pathways that are implicated in the development and progression of diabetic kidney disease, including oxidative stress, inflammation, hypertrophy, and podocyte function. This review will examine these direct and indirect actions of PPAR agonists in the diabetic kidney and explore recent findings of clinical trials of PPAR agonists in patients with diabetes.

scholarly journals Common Drug Pipelines for the Treatment of Diabetic Nephropathy and Hepatopathy: Can We Kill Two Birds with One Stone?

2020 ◽  
Vol 21 (14) ◽  
pp. 4939
Author(s):  
Yoshio Sumida ◽  
Masashi Yoneda ◽  
Hidenori Toyoda ◽  
Satoshi Yasuda ◽  
Toshifumi Tada ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
The United States ◽  
Severe Form ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Cross Sectional ◽  
Common Drug ◽  
Glucagon Like Peptide 1 ◽  
Peroxisome Proliferator Activated Receptors ◽  
Stage Renal Disease

Type 2 diabetes (T2D) is associated with diabetic nephropathy as well as nonalcoholic steatohepatitis (NASH), which can be called “diabetic hepatopathy or diabetic liver disease”. NASH, a severe form of nonalcoholic fatty disease (NAFLD), can sometimes progress to cirrhosis, hepatocellular carcinoma and hepatic failure. T2D patients are at higher risk for liver-related mortality compared with the nondiabetic population. NAFLD is closely associated with chronic kidney disease (CKD) or diabetic nephropathy according to cross-sectional and longitudinal studies. Simultaneous kidney liver transplantation (SKLT) is dramatically increasing in the United States, because NASH-related cirrhosis often complicates end-stage renal disease. Growing evidence suggests that NAFLD and CKD share common pathogenetic mechanisms and potential therapeutic targets. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH and diabetic nephropathy/CKD. There are no approved therapies for NASH, but a variety of drug pipelines are now under development. Several agents of them can also ameliorate diabetic nephropathy/CKD, including peroxisome proliferator-activated receptors agonists, apoptosis signaling kinase 1 inhibitor, nuclear factor-erythroid-2-related factor 2 activator, C-C chemokine receptor types 2/5 antagonist and nonsteroidal mineral corticoid receptor antagonist. This review focuses on common drug pipelines in the treatment of diabetic nephropathy and hepatopathy.

scholarly journals PPARs and Myocardial Infarction

2020 ◽  
Vol 21 (24) ◽  
pp. 9436
Author(s):  
Kay-Dietrich Wagner ◽  
Nicole Wagner
Keyword(s):  
Myocardial Infarction ◽  
Therapeutic Potential ◽  
Pathological Condition ◽  
Expression Patterns ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Specific Expression ◽  
Ppar Agonists ◽  
Cell Type Specific Expression ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone receptor family. They are ligand-activated transcription factors and exist in three different isoforms, PPARα (NR1C1), PPARβ/δ (NR1C2), and PPARγ (NR1C3). PPARs regulate a variety of functions, including glucose and lipid homeostasis, inflammation, and development. They exhibit tissue and cell type-specific expression patterns and functions. Besides the established notion of the therapeutic potential of PPAR agonists for the treatment of glucose and lipid disorders, more recent data propose specific PPAR ligands as potential therapies for cardiovascular diseases. In this review, we focus on the knowledge of PPAR function in myocardial infarction, a severe pathological condition for which therapeutic use of PPAR modulation has been suggested.

MO479BLOOD PRESSURE CONTROL AND OUTCOMES IN DIABETIC RENAL DISEASE : EVIDENCE FROM A TUNISIAN COHORT

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Boukhtioua Mariem ◽  
Mami Ikram ◽  
Tlili Syrine ◽  
Ghabi Hiba ◽  
Hela Jbali ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Diabetic Nephropathy ◽  
Renal Disease ◽  
Urinary Albumin Excretion ◽  
Pressure Control ◽  
Urinary Albumin ◽  
Patients With Diabetes ◽  
Group B ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background and Aims Diabetic nephropathy (DN) is associated with a high incidence of cardiovascular morbidity and mortality. The relationship between hypertension and diabetic nephropathy is complex and blood pressure (BP) control is an important management strategy in the prevention of its onset and progression .The aim of this study was to determine whether blood pressure control delays the progression of DN and prevents macrovascular complications in patients with diabetes mellitus. Method Hypertension guidelines advocate treating systolic blood pressure to less than 130 mm Hg and diastolic blood pressure to less than 80 mmHg for patients with diabetes mellitus and overt nephropathy.The relationship between blood pressure and progression of nephropathy was studied in 120 diabetic and hypertensive patients with established diabetic nephropathy. We divided hypertensive patients with stage 1 to 3 CKD already treated with antihypertensive therapy into 2 groups: those with BP < 130/80 mmHg were designated as Group A (n=66) and those with BP> 130/80 as Group B (n=54). Serum creatinine level as well as urinary albumin excretion were measured at 3 months,6 months, one year,2 years and at last visit during follow-up.The GFR was calculated using the Modification of diet in renal disease formula.The kidney disease outcome was defined as time to end-stage renal disease. The cardiovascular outcome was defined as time to myocardial infarction, stroke,ischemic stroke, hospitalization for heart failure, or revascularization. Results During the mean follow up period of 33,8 ± 11,7 months, the primary end point of end-stage renal disease occured in 9 patients (7 patients in Group B versus 2 patients in groupe A) while 11 hypertensive patient experienced a cardiovascular event.  The decline rate in GFR was significantly more important in groupe B (p<0,05). However, little difference existed between the two groups in urinary albumin excretion. Blood pressure control was not associated with improved cardiovascular outcomes when comparing the two groups. Conclusion The results of our study indicate that an uncontrolled hypertension is associated with a rapid progression of kidney impairment in diabetic patients with overt nephropathy but no relationship with the incidence of cradiovascular events was seen in our population.

scholarly journals Role of peroxisome proliferator-activated receptors in the control of alcohol dependence and concomitant liver pathology

2019 ◽  
Vol 16 (2) ◽  
pp. 244-256
Author(s):  
I. N. Semenenya ◽  
A. H. Shlyahtun ◽  
H. F. Raduta
Keyword(s):  
Liver Disease ◽  
Alcohol Dependence ◽  
Alcoholic Liver Disease ◽  
Therapeutic Potential ◽  
Scattered Data ◽  
Peroxisome Proliferator ◽  
Liver Pathology ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors

The article is aimed to summarize the scattered data on the role of peroxisome proliferator-activated receptors (PPAR) and the possibility of using PPAR’s agonists for treatment of alcohol dependence and alcoholic liver disease. Earlier it was shown that some PPAR agonists can reduce ethanol consumption and preference in rodents. Several hypotheses considering the antialcoholic activity of PPAR agonists and the roles of PPAR in the development of alcohol dependence were discussed. In light of these data, the therapeutic potential of PPARs agonists as an agent for the treatment of alcoholism, has been reviewed.

scholarly journals The Podocyte in Diabetic Kidney Disease

2009 ◽  
Vol 9 ◽  
pp. 1127-1139 ◽  
Author(s):  
Erin Stitt-Cavanagh ◽  
Laura MacLoed ◽  
Chris R.J. Kennedy
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Renin Angiotensin System ◽  
Peroxisome Proliferator ◽  
Diabetic Kidney ◽  
Cellular Hypertrophy ◽  
Treatment And Prevention ◽  
Filtration Barrier ◽  
Peroxisome Proliferator Activated Receptors ◽  
Stage Renal Disease

Approaching epidemic levels, diabetic kidney disease (DKD) is now the leading cause of end-stage renal disease (ESRD). Microalbuminuria is an early clinical marker of DKD that results from damage to the glomerular filtration barrier at the level of the highly differentiated glomerular podocyte cells. Injury to these epithelial cells, podocytopathies, includes cellular hypertrophy, foot process effacement, detachment from the glomerular basement membrane, and apoptosis. Here we review the role of a number of recently identified factors that contribute to podocytopathies in DKD. These factors include members of the renin-angiotensin system (RAS), including angiotensin-converting enzyme (ACE) types 1 and 2, prorenin and its receptor, reactive oxygen species (ROS), prostanoids, peroxisome proliferator-activated receptors (PPAR), advanced glycation end-products (AGEs) and their receptors (RAGE), adiponectin, and microRNAs. As the number of therapeutic options that slow, but do not halt, the progression of DKD to ESRD remains limited, a more comprehensive understanding of the signaling events that contribute to this increasingly prevalent disease may identify novel avenues for treatment and prevention.

scholarly journals Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Nur Samsu
Keyword(s):  
Blood Pressure ◽  
Diabetic Nephropathy ◽  
Renin Angiotensin System ◽  
Pressure Control ◽  
Therapeutic Interventions ◽  
Diagnosis And Treatment ◽  
Chronic Hyperglycemia ◽  
Classic Pattern ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Chronic hyperglycemia and high blood pressure are the main risk factors for the development of DN. In general, screening for microalbuminuria should be performed annually, starting 5 years after diagnosis in type 1 diabetes and at diagnosis and annually thereafter in type 2 diabetes. Standard therapy is blood glucose and blood pressure control using the renin-angiotensin system blockade, targeting A 1 c < 7 % , and <130/80 mmHg. Regression of albuminuria remains an important therapeutic goal. However, there are problems in diagnosis and treatment of nonproteinuric DN (NP-DN), which does not follow the classic pattern of DN. In fact, the prevalence of DN continues to increase, and additional therapy is needed to prevent or ameliorate the condition. In addition to conventional therapies, vitamin D receptor activators, incretin-related drugs, and therapies that target inflammation may also be promising for the prevention of DN progression. This review focuses on the role of inflammation and oxidative stress in the pathogenesis of DN, approaches to diagnosis in classic and NP-DN, and current and emerging therapeutic interventions.

New trends in the pharmacological intervention of PPARs in obesity: Role of natural and synthetic compounds_

2020 ◽  
Vol 28 ◽  
Author(s):  
Seyed Mohammad Nabavi ◽  
Kasi Pandima Devi ◽  
Sethuraman Sathya ◽  
Ana Sanches-Silva ◽  
Listos Joanna ◽  
...  
Keyword(s):  
Tissue Expression ◽  
Health Concern ◽  
Pharmacological Intervention ◽  
Peroxisome Proliferator ◽  
Expression Of Genes ◽  
Ppar Agonists ◽  
Prevalence Of Obesity ◽  
Peroxisome Proliferator Activated Receptors ◽  
Natural And Synthetic

: Obesity is a major health concern for a growing fraction of the population, with the prevalence of obesity and its related metabolic disorders not being fully understood. Over the last decade, many attempts have been undertaken to understand the mechanisms at the basis of this condition, in which the accumulation of fat occurring in adipose tissue, leads to the pathogenesis of obesity related disorders. Among the most recent studies, those on Peroxisome Proliferator Activated Receptors (PPARs) revealed that these nuclear receptor proteins acting as transcription factors, among others, regulate the expression of genes involved in energy, lipid, and glucose metabolisms, and chronic inflammation. The three different isotypes of PPARs, with different tissue expression and ligand binding specificity, exert similar or overlapping functions directly or indirectly linked to obesity. In this study, we reviewed the available scientific reports concerning the PPARs structure and functions, especially in obesity, considering both natural and synthetic ligands and their role in the therapy of obesity and obesity-associated disorders. In the whole, the collected data show that there are both natural and synthetic compounds that show beneficial promising activity as PPAR agonists in chronic diseases related to obesity.

scholarly journals Role of Nutrient-Sensing Signals in the Pathogenesis of Diabetic Nephropathy

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Shinji Kume ◽  
Daisuke Koya ◽  
Takashi Uzu ◽  
Hiroshi Maegawa
Keyword(s):  
Diabetic Nephropathy ◽  
Therapeutic Potential ◽  
Nutrient Sensing ◽  
Tubular Cells ◽  
New Findings ◽  
Proximal Tubular ◽  
Stage Renal Disease ◽  
End Stage ◽  
Autophagy Activity

Diabetic nephropathy is the leading cause of end-stage renal disease worldwide. The multipronged drug approach still fails to fully prevent the onset and progression of diabetic nephropathy. Therefore, a new therapeutic target to improve the prognosis of diabetic nephropathy is urgently required. Nutrient-sensing signals and their related intracellular machinery have evolved to combat prolonged periods of starvation in mammals; and these systems are conserved in the kidney. Recent studies have suggested that the activity of three nutrient-sensing signals, mTORC1, AMPK, and Sirt1, is altered in the diabetic kidney. Furthermore, autophagy activity, which is regulated by the above-mentioned nutrient-sensing signals, is also altered in both podocytes and proximal tubular cells under diabetic conditions. Under diabetic conditions, an altered nutritional state owing to nutrient excess may disturb cellular homeostasis regulated by nutrient-responsible systems, leading to exacerbation of organelle dysfunction and diabetic nephropathy. In this review, we discuss new findings showing relationships between nutrient-sensing signals, autophagy, and diabetic nephropathy and suggest the therapeutic potential of nutrient-sensing signals in diabetic nephropathy.

scholarly journals Peroxisome Proliferator-Activated Receptors: “Key” Regulators of Neuroinflammation after Traumatic Brain Injury

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Philip F. Stahel ◽  
Wade R. Smith ◽  
Jay Bruchis ◽  
Craig H. Rabb
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Cell Death ◽  
Synthetic Cannabinoids ◽  
Experimental Studies ◽  
Neuronal Cell ◽  
Peroxisome Proliferator ◽  
Therapeutic Concept ◽  
Anti Inflammatory ◽  
Peroxisome Proliferator Activated Receptors

Traumatic brain injury is characterized by neuroinflammatory pathological sequelae which contribute to brain edema and delayed neuronal cell death. Until present, no specific pharmacological compound has been found, which attenuates these pathophysiological events and improves the outcome after head injury. Recent experimental studies suggest that targeting peroxisome proliferator-activated receptors (PPARs) may represent a new anti-inflammatory therapeutic concept for traumatic brain injury. PPARs are “key” transcription factors which inhibit NFκBactivity and downstream transcription products, such as proinflammatory and proapoptotic cytokines. The present review outlines our current understanding of PPAR-mediated neuroprotective mechanisms in the injured brain and discusses potential future anti-inflammatory strategies for head-injured patients, with an emphasis on the putative beneficial combination therapy of synthetic cannabinoids (e.g., dexanabinol) with PPARαagonists (e.g., fenofibrate).

Sign in / Sign up

Export Citation Format

Share Document