Exercise training improves erectile dysfunction in diabetes: role of central mech

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Project Title: Exercise training improves erectile dysfunction in diabetes: role of central mech
Principal Investigators (PI): PATEL KAUSHIK P
Project Number: 1R01DK082956-01
Organization: UNIVERSITY OF NEBRASKA MEDICAL CENTER
 
Project Description:
[unreadable] (provided by applicant): Erectile dysfunction is a serious and common complication of diabetes mellitus. Apart from peripheral actions of corporal smooth muscle relaxation, the activation of sympathetic and parasympathetic nerves involved central mechanisms are also responsible for penile erection. We have shown that 1) in rats with streptozotocin (STZ)-induced type I diabetes (T1D) the erectile response to central administrated N-methyl-D-aspartic acid (NMDA) in the PVN is blunted, 2) NMDA-induced erection is nitric oxide (NO)-mediated, 3) neuronal NO synthase (nNOS) in the PVN of T1D rats is reduced, 4) replacing nNOS specifically in the PVN (via adenoviral-mediated gene transfer) restores the NMDA- induced erection in T1D rats, 5) plasma levels of angiotensin II (Ang II) are increased and Ang II type 1 (AT1) receptors in the PVN are up-regulated in T1D rats, 6) Ang II modulates autonomic outflow via a reactive oxygen species (ROS), particularly superoxide (O2-) mechanism, 7) Ang II down-regulates nNOS in cultured neuronal cells. Exciting preliminary results obtained in our laboratory suggest that exercise training (ExT) dramatically improves central NMDA-induced erectile response in T1D. Based on these intriguing preliminary data and previous work, the present project will attempt to address the hypothesis that ExT improves central NMDA- induced erectile dysfunction in T1D rats by regulating NO and Ang II-O2- signaling pathways in the PVN. In Aim 1 we will determine the impact of ExT on central NMDA-NO-induced erectile dysfunction in T1D rats. In Aim 2 we will determine the contribution of Ang II to central NMDA-NO- induced erectile dysfunction in T1D rats. In Aim 3 we will determine if the enhanced Ang II contributes to central NMDA-NO-induced erectile dysfunction in T1D rats via stimulation of O2-. In Aim 4 we will determine if ExT has beneficial effects on central NMDA-NO-induced erectile dysfunction through the actions on Ang II-O2- signaling in the PVN of T1D rats. These aims will be addressed in T1D rats using complementary methodologies in the whole animal to the cellular level; physiological measurement of erectile function, microinjection of the PVN in conscious and anesthetized animals, adenoviral gene transfection, O2- and NO metabolite measurements, immunohistochemistry, molecular biology techniques to measure mRNA message using real time PCR and Western blot to measure the protein within specific brain nuclei. The successful completion of the proposed studies should provide significant new information regarding the central mechanisms, specifically within the PVN of the hypothalamus, involved in altered neural regulation of erectile function and the therapeutic benefits of ExT on erectile dysfunction in T1D. Understanding the role of central mechanisms, (not much studied to date), in the altered neural drive would enhance our ability to treat the diabetic sexual dysfunction. PUBLIC HEALTH RELEVANCE: Erectile dysfunction is a serious and common complication of diabetes mellitus. The proposed mechanisms for erectile dysfunction in diabetes include both peripheral and central abnormalities However, in diabetic male patients sildenafil (Viagra) appears to be therapeutic only in 50% of the patients at the level of the penis. The proposed studies should provide significant new information regarding the central mechanisms involved in altered neural regulation of erectile function and the therapeutic benefits of exercise training on erectile dysfunction in diabetes. Understanding the role of central mechanisms, (not much studied to date), in the altered neural drive would enhance our ability to treat the diabetic sexual dysfunction. [unreadable] [unreadable] [unreadable]
 
Project Terms:
2-Deoxy-2-((methylnitrosoamino)carbonyl)amino-D-glucose 2-deoxy-2-(3-methyl-3-nitrosoureido)-D-glucopyranose 2-deoxy-2-[[(methylnitrosamino)-carbonyl]amino]-D-glucopyranose ACE Inhibitors ANG-(1-8)Octapeptide Abbott brand of sildenafil citrate Active Oxygen Address AngII Angiotensin AT1 Receptor Angiotensin Converting Enzyme Angiotensin I-Converting Enzyme Angiotensin I-Converting Enzyme Inhibitors Angiotensin II Angiotensin II Type 1 Receptor Angiotensin-(1-8) Octapeptide Angiotensin-Converting Enzyme Inhibitors Animals Antagonists, Angiotensin-Converting Enzyme Biochemical Biochemical Genetics Blood Plasma Blotting, Western Brain CD143 Antigens CNOS Carboxycathepsin Cell Communication and Signaling Cell Nucleus Cell Signaling Cell/Tissue, Immunohistochemistry Cells Chronic Common Rat Strains Complications of Diabetes Mellitus Conscious Consciousness Constitutive NOS Data Diabetes Complications Diabetes Mellitus Diabetes Mellitus, Brittle Diabetes Mellitus, Insulin-Dependent Diabetes Mellitus, Juvenile-Onset Diabetes Mellitus, Ketosis-Prone Diabetes Mellitus, Sudden-Onset Diabetes Mellitus, Type 1 Diabetes Mellitus, Type I Diabetes-Related Complications Diabetic Complications Dipeptidyl Peptidase A Dysfunction EC 1.14.13.39 ECNOS EDRF Synthase ENOS Elements Encephalon Encephalons Endogenous Nitrate Vasodilator Endothelial NOS Endothelial Nitric Oxide Synthase Endothelial Nitric Oxide Synthase 3 Endothelium-Derived Growth Factor Synthase Endothelium-Derived Relaxing Factor Enzyme Inhibition Erectile dysfunction Erythrocuprein Exercise Exercise, Physical Functional disorder Gene Transfer Genes Genetic Genetic, Biochemical Genital System, Male, Penis Guanylyl Cyclase-Activating Factor Synthase Hemocuprein Hyperglycemia Hypothalamic structure Hypothalamus IDD IDDM IHC Immunohistochemistry Immunohistochemistry Staining Method Infusion Infusion procedures Insulin-Dependent Diabetes Mellitus Intracellular Communication and Signaling Kininase A Kininase II Kininase II Antagonists Kininase II Inhibitors L-Arginine,NADPH[{..}]oxygen oxidoreductase (nitric-oxide-forming) Laboratories Mammals, Rats Measurement Measures Mediating Medulla Spinalis Messenger RNA Method LOINC Axis 6 Methodology Methods Microinjections Molecular Molecular Biology Techniques Mononitrogen Monoxide Muscle Relaxation Muscle relaxation phase Muscle, Involuntary Muscle, Smooth N Methyl D aspartic Acid N methyl D aspartate N-Methyl-D-aspartate N-Methylaspartate NADPH-Diaphorase NMDA NO Synthase NOS 1 protein NOS Type III NOS3 NOS3 protein, human NOSIII Nerve Nerve Cells Nerve Unit Nervous Nervous System, Brain Neural Cell Neural Constitutive Nitric Oxide Synthase Neural Pathways Neurocyte Neurons Nitric Oxide Nitric Oxide Synthase Nitric Oxide Synthase 3 Nitric Oxide Synthase Type I Nitric Oxide, Endothelium-Derived Nitric-Oxide Synthetase Nitrogen Monoxide Nitrogen Protoxide Nitrogen oxide Nucleus OXT Ocytocin Oxidases Oxygen Radicals Oxytocin PDE Paraventricular Hypothalamic Nucleus Paraventricular Nucleus Patients Penile Erection Peptidyl-Dipeptidase A Peripheral Pfizer brand of sildenafil citrate Phosphodiesterases Physiologic Physiological Physiopathology Plasma Pro-Oxidants Proteins RNA, Messenger Rat Rattus Reactive Oxygen Species Receptor Protein Receptor, Angiotensin, Type 1 Recombinant Oxytocin Regulation Reticuloendothelial System, Serum, Plasma Role SOD STZ Sedentary Exercise Serum, Plasma Sex Disorders Sexual Dysfunction Signal Pathway Signal Transduction Signal Transduction Systems Signaling Smooth muscle (tissue) Spinal Cord Stimulus Streptozocin Streptozotocin Structure of paraventricular nucleus Superoxide Anion Superoxide Dismutase Superoxide Radical Superoxide[{..}]superoxide oxidoreductase Superoxides System System, LOINC Axis 4 T1 diabetes T1D T1DM Testing Therapeutic Time Training Transfection Type 1 diabetes Very Light Activity Very Light Exercise Viagra Western Blotting Western Blottings Western Immunoblotting Work Zanosar adenoviral-mediated autonomic neuropathy base biological signal transduction cytocuprein diabetes diabetic diabetic patient eNOS enzyme endothelial cell derived relaxing factor endothelial constitutive nitric oxide synthase erection gene product human NOS3 protein hyperglycemic hypothalamic improved inhibitor inhibitor/antagonist insight insulin dependent diabetes juvenile diabetes juvenile diabetes mellitus ketosis prone diabetes mRNA male mimetics nNOS enzyme neural neural control neural regulation neuronal neuronal nitric oxide synthase neuroregulation paraventricular nucleus pathophysiology penis penis erection phosphoric diester hydrolase protein blotting public health relevance receptor receptor expression relating to nervous system response sildenafil social role transfer of a gene type I diabetes
Project Title: Exercise training improves erectile dysfunction in diabetes: role of central mech
Principal Investigators (PI): PATEL KAUSHIK P
Project Number: 1R01DK082956-01
Organization: UNIVERSITY OF NEBRASKA MEDICAL CENTER
 
Project Categories:
• Natural Sciences > Aging Diseases and Pathology > Neurodegenerative diseases > Amyotrophic lateral sclerosis
 
Other Information:
Fiscal Year: 2009
Project Start Date: 1 April 2009
Project End Date: 28 February 2013
Administering Institute Or Center: DK
 
Project Funding Information:
Total Funding: $356,400
Year Funding Organization Total Funding, $
2009 NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES $356,400
Project Title: Exercise training improves erectile dysfunction in diabetes: role of central mech
Principal Investigators (PI): PATEL KAUSHIK P
Project Number: 1R01DK082956-01
Organization: UNIVERSITY OF NEBRASKA MEDICAL CENTER
 
Project_number Title Year FY Total Cost
There are no results for this project in database.
Project Title: Exercise training improves erectile dysfunction in diabetes: role of central mech
Principal Investigators (PI): PATEL KAUSHIK P
Project Number: 1R01DK082956-01
Organization: UNIVERSITY OF NEBRASKA MEDICAL CENTER
 
Project number Project title Organization FY Funding Organization FY Total Cost
1R01DK082956-01Exercise training improves erectile dysfunction in diabetes: role of central mechUNIVERSITY OF NEBRASKA MEDICAL CENTER2009NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
$356,400
Project Title: Exercise training improves erectile dysfunction in diabetes: role of central mech
Principal Investigators (PI): PATEL KAUSHIK P
Project Number: 1R01DK082956-01
Organization: UNIVERSITY OF NEBRASKA MEDICAL CENTER
 
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Project Title: Exercise training improves erectile dysfunction in diabetes: role of central mech
Principal Investigators (PI): PATEL KAUSHIK P
Project Number: 1R01DK082956-01
Organization: UNIVERSITY OF NEBRASKA MEDICAL CENTER
 
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