Diabetes-associated Erectile Dysfunction

2009 ◽  
Vol 05 (0) ◽  
pp. 75 ◽  
Author(s):  
Pedro Vendeira ◽  
Carla Costa ◽  
Ronald Virag ◽  
◽  
◽  
...  
Keyword(s):  
Risk Factor ◽  
Erectile Dysfunction ◽  
Endothelial Dysfunction ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Experimental Models ◽  
Vascular Pathology ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Endothelial Cell Function ◽  
The Metabolic Syndrome

Erectile dysfunction (ED) is a common complication of diabetes, with a prevalence ranging from 15 to 55%. The basis underlying diabetesassociated ED is multifactorial, involving changes in peripheral nerve activity and alterations in endothelial cell function. Due to the complexity of this pathology, the development of experimental models has been crucial in evaluating and translating fundamental results into clinical diabetes-associated ED. The concept of hard-to-treat patients, such as men with diabetes, is now fully accepted due to the complex mechanisms involved. In these men, the response to common oral treatments with phosphodiesterase type 5 inhibitors (PDE5Is) is far from desired, and maximal doses of the drugs are often needed. In addition, diabetes is commonly associated with other co-morbidities, such as hypertension, hypercholesterolaemia and obesity, clusters of the metabolic syndrome (MetS). ED is considered an early warning sentinel for coronary artery disease, just as endothelial dysfunction is seen as a major risk factor for ED. Testosterone deficiency syndrome, a very common syndrome in diabetes and MetS, has been shown to be an independent determinant of endothelial dysfunction, thus contributing to vascular pathology, including ED. This syndrome should be identified among patients, and therapeutic intervention may be required. PDE5Is may improve erectile function with or without the help of other second- or third-line treatments. Other strategies to maximise the response to PDE5Is include risk factor modification and daily dosing of the drugs, instead of on-demand treatment. However, better understanding of the fundamental molecular mechanisms underlying diabetes-associated ED is essential to improving and developing more effective therapies.

scholarly journals Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia

2017 ◽  
Vol 232 (1) ◽  
pp. R27-R44 ◽  
Author(s):  
D S Boeldt ◽  
I M Bird
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Cell Function ◽  
Endothelial Cell Dysfunction ◽  
Hypertensive Disorders Of Pregnancy ◽  
Endothelial Cell Function ◽  
Vascular Adaptation ◽  
Cell Dysfunction ◽  
Maternal Adaptation ◽  
Flow Through

Maternal vascular adaptation to pregnancy is critically important to expand the capacity for blood flow through the uteroplacental unit to meet the needs of the developing fetus. Failure of the maternal vasculature to properly adapt can result in hypertensive disorders of pregnancy such as preeclampsia (PE). Herein, we review the endocrinology of maternal adaptation to pregnancy and contrast this with that of PE. Our focus is specifically on those hormones that directly influence endothelial cell function and dysfunction, as endothelial cell dysfunction is a hallmark of PE. A variety of growth factors and cytokines are present in normal vascular adaptation to pregnancy. However, they have also been shown to be circulating at abnormal levels in PE pregnancies. Many of these factors promote endothelial dysfunction when present at abnormal levels by acutely inhibiting key Ca2+ signaling events and chronically promoting the breakdown of endothelial cell–cell contacts. Increasingly, our understanding of how the contributions of the placenta, immune cells, and the endothelium itself promote the endocrine milieu of PE is becoming clearer. We then describe in detail how the complex endocrine environment of PE affects endothelial cell function, why this has contributed to the difficulty in fully understanding and treating this disorder, and how a focus on signaling convergence points of many hormones may be a more successful treatment strategy.

scholarly journals Methylglyoxal triggers human aortic endothelial cell dysfunction via modulation of the KATP/MAPK pathway

2019 ◽  
Vol 317 (1) ◽  
pp. C68-C81 ◽  
Author(s):  
Yihan Wang ◽  
Leo M. Hall ◽  
Marisa Kujawa ◽  
Hainan Li ◽  
Xiang Zhang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Network Formation ◽  
Cell Function ◽  
Mapk Pathway ◽  
Endothelial Cell Dysfunction ◽  
Endothelial Cell Function ◽  
Cell Dysfunction ◽  
Type 2 Diabetic

Endothelial dysfunction is a key risk factor in diabetes-related multiorgan damage. Methylglyoxal (MGO), a highly reactive dicarbonyl generated primarily as a by-product of glycolysis, is increased in both type 1 and type 2 diabetic patients. MGO can rapidly bind with proteins, nucleic acids, and lipids, resulting in structural and functional changes. MGO can also form advanced glycation end products (AGEs). How MGO causes endothelial cell dysfunction, however, is not clear. Human aortic endothelial cells (HAECs) from healthy (H-HAECs) and type 2 diabetic (D-HAECs) donors were cultured in endothelial growth medium (EGM-2). D-HAECs demonstrated impaired network formation (on Matrigel) and proliferation (MTT assay), as well as increased apoptosis (caspase-3/7 activity and TUNEL staining), compared with H-HAECs. High glucose (25 mM) or AGEs (200 ng/ml) did not induce such immediate, detrimental effects as MGO (10 µM). H-HAECs were treated with MGO (10 µM) for 24 h with or without the ATP-sensitive potassium (KATP) channel antagonist glibenclamide (1 µM). MGO significantly impaired H-HAEC network formation and proliferation and induced cell apoptosis, which was reversed by glibenclamide. Furthermore, siRNA against the KATP channel protein Kir6.1 significantly inhibited endothelial cell function at basal status but rescued impaired endothelial cell function upon MGO exposure. Meanwhile, activation of MAPK pathways p38 kinase, c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) (determined by Western blot analyses of their phosphorylated forms, p-JNK, p-p38, and p-ERK) in D-HAECs were significantly enhanced compared with those in H-HAECs. MGO exposure enhanced the activation of all three MAPK pathways in H-HAECs, whereas glibenclamide reversed the activation of p-stress-activated protein kinase/JNK induced by MGO. Glyoxalase-1 (GLO1) is the endogenous MGO-detoxifying enzyme. In healthy mice that received an inhibitor of GLO1, MGO deposition in aortic wall was enhanced and endothelial cell sprouting from isolated aortic segment was significantly inhibited. Our data suggest that MGO triggers endothelial cell dysfunction by activating the JNK/p38 MAPK pathway. This effect arises partly through activation of KATP channels. By understanding how MGO induces endothelial dysfunction, our study may provide useful information for developing MGO-targeted interventions to treat vascular disorders in diabetes.

Acupuncture and Neurostimulation Therapy for Erectile Dysfunction in the Patients with the Metabolic Syndrome

10.12737/9074 ◽  
2015 ◽  
Vol 22 (1) ◽  
pp. 38-46
Author(s):  
Долаев ◽  
R. Dolaev
Keyword(s):  
Metabolic Syndrome ◽  
Electrical Stimulation ◽  
Erectile Dysfunction ◽  
Endothelial Dysfunction ◽  
Therapeutic Effect ◽  
Biochemical Markers ◽  
The Metabolic Syndrome ◽  
Treat Ment ◽  
Integrated Indicators ◽  
Stimulation Of

There were 40 patients with a metabolic syndrome with erectile dysfunction under observation. All patients received physiotherapy exercises, psychotherapeutic correction of a sex disadaptation, epicutaneous electrical stimulation of cavernous bodies of a penis and muscles of a pelvic bottom, and acupuncture according to specially developed scheme. It is proved that the combination of medical methods provides duration of therapeutic effect after course of treat-ment. Normalization of integrated indicators of the International index of erectile function came at 72,5% of patients. Vegetative indicators reached values of norm at 72,5% of patients, normalization of volume of a prostate came at 72,5% of patients, a prostate hemodynamic – at 70% of patients. The penil hemodynamic was normalized at 72,5% of patients. Normalization of functional activity hypothalamic – adrenal and testicular system came at 70% of patients. Components of a copulative cycle reached values of norm at 70% of patients. Carbohydrate metabolism was normalized at 75%, lipide – at 72,5%, biochemical markers of endothelial dysfunction – at 72,5% of patients, the index of exacerbations of a metabolic syndrome decreased by 1,9 times. The remote results of therapeutic effect in 1 year after treatment showed that appreciable improvement was observed at 55%, improvement – at 25%, without improvement – at 20% of patients.

scholarly journals Erectile dysfunction in men with diabetes (literature review) Part 1

2021 ◽  
Vol 17 (5) ◽  
pp. 426-434
Author(s):  
E.V. Luchytskyy ◽  
V.Ye. Luchytskiy
Keyword(s):  
Quality Of Life ◽  
Diabetes Mellitus ◽  
Risk Factor ◽  
Erectile Dysfunction ◽  
Rating Scale ◽  
Sexual Experience ◽  
Clinical Manifestations ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Patients With Diabetes

The first part of the review article highlights modern views on the prevalence, etiology and features of the pathogenesis of erectile dysfunction (ED) in men with diabetes mellitus. Google Scholar and PubMed databases were used to search for literature sources. The role of comorbid diseases in the development of ED in men with diabetes mellitus has been shown. The generalized data on the main clinical manifestations of erectile dysfunction, methods of its diagnosis and treatment are given. A number of epidemiological studies over the past 20 years have found that erectile dysfunction in men with diabetes may be an early marker of cardiovascular complications. Thus, in the algorithm for ED diagnosis in patients with diabetes it is necessary to conduct a thorough examination of the cardiovascular system. Numerous literature sources indicate an important role in the correction of androgen deficiency in men with type 2 diabetes, in order to enhance the effectiveness of phosphodiesterase type 5 inhibitors. Erectile dysfunction involves a change in any of the components of an erectile response. ED can negatively affect a man’s quality of life because most patients experience symptoms of depression and anxiety related to their sexual capabilities. These symptoms also affect a partner’s sexual experience and the couple’s quality of life. Clinical features of ED have many key features in the anamnesis, including some physical signs during examination depending on a type of diabetes. With age, comorbid conditions play an increasing role in the development of ED. Diabetes mellitus, cardiovascular diseases, obesity can lead to the development of ED before accelerated deterioration of erectile function and disorders at the molecular level of the mechanisms underlying erection. Patients with diabetes and ED have higher scores on the depression rating scale, and poorer overall health and quality of life. Early detection of ED in individuals with diabetes can improve the overall health and quality of life of patients. Patients with diabetes with poor glycemic control and older age are more likely to develop severe ED, which further exacerbates an already compromised health and quality of life. According to the National Health and Nutrition Examination Survey (2001–2002), diabetes mellitus is a modified risk factor independently associated with the development of ED (odds ratio (OR) 2.69), obesity (OR 1.60), smoking (OR 1.74) and hypertension (OR 1.56). Erectile dysfunction is a common complication of diabetes, and diabetes is a risk factor for ED; men with diabetes are three times more likely to have ED.

scholarly journals Diet-induced alteration of intestinal stem cell function underlies obesity and prediabetes in mice

2021 ◽  
Vol 3 (9) ◽  
pp. 1202-1216
Author(s):  
Alexandra Aliluev ◽  
Sophie Tritschler ◽  
Michael Sterr ◽  
Lena Oppenländer ◽  
Julia Hinterdobler ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cell Function ◽  
Hormone Secretion ◽  
Cell Types ◽  
Acid Synthesis ◽  
Enteroendocrine Cell ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Ppar Signaling ◽  
Obesogenic Diet

AbstractExcess nutrient uptake and altered hormone secretion in the gut contribute to a systemic energy imbalance, which causes obesity and an increased risk of type 2 diabetes and colorectal cancer. This functional maladaptation is thought to emerge at the level of the intestinal stem cells (ISCs). However, it is not clear how an obesogenic diet affects ISC identity and fate. Here we show that an obesogenic diet induces ISC and progenitor hyperproliferation, enhances ISC differentiation and cell turnover and changes the regional identities of ISCs and enterocytes in mice. Single-cell resolution of the enteroendocrine lineage reveals an increase in progenitors and peptidergic enteroendocrine cell types and a decrease in serotonergic enteroendocrine cell types. Mechanistically, we link increased fatty acid synthesis, Ppar signaling and the Insr–Igf1r–Akt pathway to mucosal changes. This study describes molecular mechanisms of diet-induced intestinal maladaptation that promote obesity and therefore underlie the pathogenesis of the metabolic syndrome and associated complications.

Vascular pathophysiology of hypertension

2017 ◽  
Author(s):  
Tomasz J. Guzik ◽  
Rhian M. Touyz
Keyword(s):  
Cardiovascular Disease ◽  
Smooth Muscle ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Smooth Muscle ◽  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Peripheral Resistance ◽  
Vascular Stiffness ◽  
Vascular Pathology

Hypertension is a multifactorial disease, in which vascular dysfunction plays a prominent role. It occurs in over 30% of adults worldwide and an additional 30% are at high risk of developing the disease. Vascular pathology is both a cause of the disease and a key manifestation of hypertension-associated target-organ damage. It leads to clinical symptoms and is a key risk factor for cardiovascular disease. All layers of the vascular wall and the endothelium are involved in the pathogenesis of hypertension. Pathogenetic mechanisms, whereby vascular damage contributes to hypertension, are linked to increased peripheral vascular resistance. At the vascular level, processes leading to change sin peripheral resistance include hyper-contractility of vascular smooth muscle cells, endothelial dysfunction, and structural remodelling, due to aberrant vascular signalling, oxidative and inflammatory responses. Increased vascular stiffness due to vascular remodelling, adventitial fibrosis, and inflammation are key processes involved in sustained and established hypertension. These mechanisms are linked to vascular smooth muscle and fibroblast proliferation, migration, extracellular matrix remodelling, calcification, and inflammation. Apart from the key role in the pathogenesis of hypertension, hypertensive vasculopathy also predisposes to atherosclerosis, another risk factor for cardiovascular disease. This is linked to increased transmural pressure, blood flow, and shear stress alterations in hypertension, as well as endothelial dysfunction and vascular stiffness. Therefore, understanding the mechanisms and identifying potential novel treatments targeting hypertensive vasculopathy are of primary importance in vascular medicine.

scholarly journals Endothelial dysfunction in pulmonary arterial hypertension: an evolving landscape (2017 Grover Conference Series)

2017 ◽  
Vol 8 (1) ◽  
pp. 204589321775291 ◽  
Author(s):  
Benoît Ranchoux ◽  
Lloyd D. Harvey ◽  
Ramon J. Ayon ◽  
Aleksandra Babicheva ◽  
Sebastien Bonnet ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Endothelial Dysfunction ◽  
Arterial Hypertension ◽  
Molecular Mechanisms ◽  
Right Heart Failure ◽  
Vascular Pathology ◽  
Mesenchymal Transition ◽  
Conference Series ◽  
Major Player ◽  
Pulmonary Arterial

Endothelial dysfunction is a major player in the development and progression of vascular pathology in pulmonary arterial hypertension (PAH), a disease associated with small vessel loss and obstructive vasculopathy that leads to increased pulmonary vascular resistance, subsequent right heart failure, and premature death. Over the past ten years, there has been tremendous progress in our understanding of pulmonary endothelial biology as it pertains to the genetic and molecular mechanisms that orchestrate the endothelial response to direct or indirect injury, and how their dysregulation can contribute to the pathogenesis of PAH. As one of the major topics included in the 2017 Grover Conference Series, discussion centered on recent developments in four areas of pulmonary endothelial biology: (1) angiogenesis; (2) endothelial-mesenchymal transition (EndMT); (3) epigenetics; and (4) biology of voltage-gated ion channels. The present review will summarize the content of these discussions and provide a perspective on the most promising aspects of endothelial dysfunction that may be amenable for therapeutic development.

Erectile Dysfunction following Radical Prostatectomy: A Review

2011 ◽  
Vol 4 (6) ◽  
pp. 227-242 ◽  
Author(s):  
Nicholas M. Pantelides ◽  
Sachin Agrawal ◽  
Chris Poullis ◽  
Andrew Chetwood ◽  
Mathias H. Winkler
Keyword(s):  
Erectile Dysfunction ◽  
Radical Prostatectomy ◽  
Molecular Mechanisms ◽  
Current Status ◽  
Nerve Sparing ◽  
Phosphodiesterase Type 5 Inhibitors ◽  
Factors Affecting ◽  
Risk Stratification Model ◽  
Smooth Muscle Function ◽  
Phosphodiesterase Type

Radical prostatectomy remains the gold-standard treatment for localised prostate cancer. Despite the widespread introduction of nerve-sparing techniques, post-operative erectile dysfunction (ED) is still a significant source of morbidity. There are multiple approaches to prevent and treat ED. Recent refinements to surgical technique attempt to minimise disruption to the prostatic neural and arterial supply. A greater understanding of the factors affecting ED has also enabled the first multi-variate risk stratification model, thereby potentially improving awareness of pre-operative risk. Numerous on-demand treatments are available, including phosphodiesterase type 5 inhibitors, intracavernous/transurethral alprostadil, vacuum erection devices and combination therapy with multiple agents. As our understanding of the aetiology improves, attempts to manipulate the molecular mechanisms underpinning ED are also being investigated. In addition, early pharmacological rehabilitation is used to preserve cavernosal smooth muscle function until intra-operative neurapraxia resolves, although the optimum regimen is yet to be defined. Currently, much work is ongoing to improve our understanding and treatment of post-prostatectomy ED. We review the current status and recent advances in this field.

scholarly journals The Role of Endothelial Dysfunction in Peripheral Blood Nerve Barrier: Molecular Mechanisms and Pathophysiological Implications

2019 ◽  
Vol 20 (12) ◽  
pp. 3022 ◽  
Author(s):  
Jessica Maiuolo ◽  
Micaela Gliozzi ◽  
Vincenzo Musolino ◽  
Cristina Carresi ◽  
Saverio Nucera ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Nervous System ◽  
Erectile Dysfunction ◽  
Endothelial Dysfunction ◽  
Peripheral Nerves ◽  
Molecular Mechanisms ◽  
Nerve Tissue ◽  
Nerve Degeneration ◽  
Peripheral Nerve Damage

The exchange of solutes between the blood and the nerve tissue is mediated by specific and high selective barriers in order to ensure the integrity of the different compartments of the nervous system. At peripheral level, this function is maintained by the Blood Nerve Barrier (BNB) that, in the presence, of specific stressor stimuli can be damaged causing the onset of neurodegenerative processes. An essential component of BNB is represented by the endothelial cells surrounding the sub-structures of peripheral nerves and increasing evidence suggests that endothelial dysfunction can be considered a leading cause of the nerve degeneration. The purpose of this review is to highlight the main mechanisms involved in the impairment of endothelial cells in specific diseases associated with peripheral nerve damage, such as diabetic neuropathy, erectile dysfunction and inflammation of the sciatic nerve.

Inhibition of pro-inflammatory cytokine receptor signalling by cAMP in vascular endothelial cells

2005 ◽  
Vol 33 (5) ◽  
pp. 1126-1128 ◽  
Author(s):  
W.A. Sands ◽  
T.M. Palmer
Keyword(s):  
Molecular Mechanisms ◽  
Cell Function ◽  
Vascular Endothelial Cell ◽  
Janus Kinase ◽  
Cytokine Receptor ◽  
Intracellular Camp ◽  
Vascular Endothelial ◽  
Endothelial Cell Function ◽  
Inhibitory Processes ◽  
Inflammatory Signalling

The anti-inflammatory effects of the prototypical second messenger cAMP have been extensively documented in multiple cell types. However, in many instances, the molecular mechanisms by which cAMP elevation disrupts specific pro-inflammatory signalling cascades are unknown. In this review, we will describe the importance of the JAK–STAT (where JAK stands for Janus kinase and STAT for signal transducer and activator of transcription) signalling pathway in vascular endothelial cell function, outline key inhibitory processes that serve to reduce cytokine-stimulated tyrosine phosphorylation and activation of STAT proteins, and discuss possible mechanisms by which intracellular cAMP sensors could interact with these inhibitory processes to diminish cytokine receptor-mediated pro-inflammatory signalling.

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