Featured Research

from universities, journals, and other organizations

Does Protein Contribute To Erectile Dysfunction Among Diabetic/Obese?

Date:
October 7, 2003
Source:
American Physiological Society
Summary:
More than eight million men are at risk for erectile dysfunction (ED) induced by Type II (insulin resistant) diabetes. While the exact mechanism(s) involved in diabetes mellitus induced erectile dysfunction (DMED) is not yet understood, a team of researchers has hypothesized that certain proteins may regulate penile vascular tone increasing sensitivity to the action of vasoconstrictor agents.

More than eight million men are at risk for erectile dysfunction (ED) induced by Type II (insulin resistant) diabetes. While the exact mechanism(s) involved in diabetes mellitus induced erectile dysfunction (DMED) is not yet understood, a team of researchers has hypothesized that certain proteins may regulate penile vascular tone increasing sensitivity to the action of vasoconstrictor agents. Their findings suggest that protein kinase C (PKC) may contribute to an enhanced vasoconstriction of the penile circulation and reduced erectile response.

Related Articles


Constriction of the penile vasculature prevents erection and is largely mediated by two agents: a-adrenergic agonists or endothelin (ET-1). These agents cause vasoconstriction by activating phospholipase C (PLC) and result in the generation of inositol triphosphate (IP3) and diacylglycerol (DAG). This pathway is believed to recruit PKC in the constrictor response. Researchers have tested the hypothesis that in diabetic-obese Zucker rats, there is a depressed erectile response caused by increased action of the vasoconstrictor pathway involving PKC in a key sensitization process.

A New Study

The authors of a new study entitled “Altered Penile Vascular Reactivity and Erection of the Zucker Rat: A Role for PKC Ca2+ Sensitization,” are Christopher J. Wingard, Delores Young, Katherine Lane and Shadhid Husain, all of the Department of Physiology, the Medical College of Georgia, Augusta, GA. They will present their findings during the upcoming scientific conference, Understanding Renal and Cardiovascular Function Through Physiological Genomics, a meeting of the American Physiological Society (APS) (http://www.the-aps.org), being held October 1-4, 2003 at the Radisson Riverfront Hotel and Convention Center, Augusta, GA.

Methodology

The researchers examined the erectile response (ICP/MAP) to pelvic ganglion stimulation using lean and obese-diabetic Zucker rats. Their methodology included:

Erectile Response Measurements: Lean or obese-diabetic male rats between 15-18 weeks of age were used. The animals were anesthetized and the left carotid artery cannulated to continuously monitor the mean arterial pressure (MAP). The right corpus cavernosum was cannulated to permit continuous monitoring of intra-cavernosal pressure (ICP) and the left corpus cavernosum was cannulated to allow for administration of vasoactive compounds. Bipolar electrodes were positioned on the right major pelvic ganglion (MPG) and, during the experiment, stimulatory voltages applied to the MPG ranged from 1 to 6 volts delivered in 5 msec pulses at a frequency of 12 Hz. The duration of stimulation was 1 minute with rest periods of 5 minutes between subsequent stimulations.

Isolated Cavernosal Tissue Force Measurements: Cavernosal strips were bathed in a physiological salt solution and gassed with breathing air. Strips were mounted at lengths that allow maximal force generation during potassium-depolarization. Cumulative dose response curves for the a-adrenergic agonist phenylephrine, (PE) 0.1-10 mM and ET-1 (0.01-10 mM) were preformed. Cumulative dose-response protocols were completed either in the absence (Control) or presence of PKC inhibitor Chelerythrine (10 mM). Tissues were incubated with the inhibitor for 30 minutes prior the completion of the dose-response protocol.

Western Blotting: Equal amounts of proteins were separated on 10% SDS-PAGE and transferred to nitrocellulose membranes followed by incubation with anti-PKC and Rho-kinase isoforms or RhoA antibodies for 3 h at 20 C. After washing, the membranes were incubated with secondary antibodies for 1 h at 20 C. For chemiluminescent detection, the membranes were treated with enhanced chemiluminescent (ECL) reagent and subsequently exposed to ECL hyperfilm.

Quantification of Protein of Interest: The densities of the protein bands were determined by scanning with a densitometer. Specific immunoreactive bands were expressed as arbitrary units (AU), which were calculated from the area of peak of selected band scanned by the densitometer. The density values were normalized to the protein content of b-actin and expressed relative to those determined from the lean tissues. Data were analyzed using analysis of variance (ANOVA) with post hoc comparisons; statistical significance was set at P < 0.05.

Results

The researchers observed that:

* erectile response of the obese animals was suppressed by >30 percent at voltages >3;

* maximal contractile response of tissues from obese-diabetic animals was increased by 25% for PE and 35% for ET-1 stimulations. However, there was no significant shift in the sensitivity to these agonists when comparing calculated EC50’s for lean and diabetic-obese tissues;

* PKC inhibitor Chelerythrine inhibited more than 70 percent of the force generated by ET-1 in tissues from the obese-diabetic animals while only blocking 30 percent of the phenylephrine induced force generation;

* obese-diabetic corpus cavernosum showed increased protein expression of PKC isozymes a, d and Rho-kinase b.

Conclusions

These results suggest that PKCs may contribute to a vasoconstriction of the penile circulation, and to reduced erectile response in the diabetic-obese Zucker rat. Future research is aimed at identifying the specific elements in the signaling pathway involving PKC and controlling the constrictive behavior of the penile vasculature. Such findings, by adding to the understanding of how constrictor agonists play a role in DMED, will eventually make a significant contribution to the treatment methods for those who display the hallmarks of obesity-induced hypertension and diabetes.

The American Physiological Society (APS) is one of the world’s most prestigious organizations for physiological scientists. These researchers specialize in understanding the processes and functions by which animals live, and thus ultimately underlie human health and disease. Founded in 1887 the Bethesda, MD-based Society has more than 11,000 members and publishes 3,800 articles in its 14 peer-reviewed journals each year.


Story Source:

The above story is based on materials provided by American Physiological Society. Note: Materials may be edited for content and length.


Cite This Page:

American Physiological Society. "Does Protein Contribute To Erectile Dysfunction Among Diabetic/Obese?." ScienceDaily. ScienceDaily, 7 October 2003. <www.sciencedaily.com/releases/2003/10/031007061615.htm>.
American Physiological Society. (2003, October 7). Does Protein Contribute To Erectile Dysfunction Among Diabetic/Obese?. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2003/10/031007061615.htm
American Physiological Society. "Does Protein Contribute To Erectile Dysfunction Among Diabetic/Obese?." ScienceDaily. www.sciencedaily.com/releases/2003/10/031007061615.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com
From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Newsy (Nov. 25, 2014) Need another reason to eat yogurt every day? Researchers now say it could reduce a person's risk of developing type 2 diabetes. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins