Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

COX-2 inhibitors and renal damage in obesity-related Type II diabetes

01.10.2003


New findings suggest altered kidney regulation of COX-2 occurs at very early stage in obesity-related diabetic nephropathy



In human diabetic patients, an excessive vasoconstrictive and pro-aggregatory thromboxane (TXA2) renal synthesis, along with a decrease in vasodilatory and anti-aggregatory prostaglandin (PGE2) synthesis, has been found to influence kidney function. Prostaglandins and thromboxane are formed by the enzymatic oxidation of arachidonic acid catalyzed by the cyclooxygenases, COX 1 and COX-2. Recently developed non-steroidal anti-inflammatory drugs (NSAIDS) are targeted to inhibit COX-2 and treat inflammation and arthritic pain. It is not known if the use of NSAIDS may be beneficial for the treatment of kidney disease; however, the upregulation of pro-inflammatory COX-2 and increased production of COX-2 derived metabolites have been implicated in diabetic nephropathy. COX-2 regulation and its association with renal damage are not known in the Obese Zucker rat. A new study tests the hypothesis that altered kidney regulation of COX-2 occurs at a very early stage in the progression of kidney disease.

A New Study


The authors of the study entitled, "Renal Microvascular COX-2 Upregulation is Associated with Kidney Damage in Zucker Obese Rats," are Aparajita Dey, Roger S. Williams, David M. Pollock, David W. Stepp and John D. Imig, all from the Vascular Biology Center, Medical College of Georgia, Augusta, GA. They are presenting their findings during the American Physiological Society (APS) (www.the-aps.org) conference, Understanding Renal and Cardiovascular Function Through Physiological Genomics. The scientific conference is being held October 1-4, 2003 at the Radisson Riverfront Hotel and Convention Center, Augusta, GA.

Background

Obesity, a major nutritional disorder in the United States, leads to the development of Type II diabetes, hypertension, atherosclerosis and chronic renal disease, most of which are interdependent factors. Diabetic nephropathy, a kidney disease that develops in as many as 20 to 40 percent of diabetics, is the leading cause of end stage renal disease (ESRD). In addition to diabetes, obesity, hypertension, hyperlipidemia and other risk factors contribute to the development and progression of kidney disease.

The Obese Zucker rat displays all the metabolic characteristics associated with Type II diabetes and hypertension, and develops extensive renal damage. Obese Zucker rats possess a mutant leptin receptor that explains their uncontrolled appetite and, consequently, results in obesity and its associated characteristics (insulin resistance, hypertension, etc.), although the mechanisms responsible for renal damage in the Obese Zucker rat remain unknown.

Methodology

Obese Zucker rats at 10-12 weeks or 20-21 weeks of age were studied. The rats were housed in separate cages and maintained in a temperature and light-controlled room. Throughout the experimental period, animals had access to standard chow and drinking water. Blood pressure was measured in the conscious state utilizing the radiotelemetry method. Blood glucose levels and body weight were measured periodically.

Protein expression of COX-1 and COX-2 in the kidney cortex, renal microvessels and glomeruli was studied. The levels of 6-keto PGF1a, PGF2a, PGE2 and TXB2 in urine were measured using enzyme immunoassays. Urinary albumin excretion, and indicator of kidney damage, was measured. Kidneys were perfusion fixed in 10% buffered formalin solution and embedded in paraffin for light microscopic evaluation.

Results

The researchers found that:
  • the Obese Zucker rats weighed 432 ± 20 g with a blood glucose of 105 ± 5 mg/dl at 10-12 weeks of age and weighed 679 ± 12 g with a blood glucose of 161 ± 13 mg/dl at 20-21 weeks of age. Blood pressure was slightly elevated in the Obese Zucker rat compared to lean rats and averaged 105 ± 5 mmHg;

  • increased COX-2 protein expression was observed in the kidney cortex and microvessels of the Obese Zucker rats at 10-12 and 20-21 weeks of age. The increase in COX-2 protein expression was associated with increases in TXB2 and decreases in PGE2 urinary excretion rates; and

  • increased urinary albumin was evident in the Obese Zucker rat at 10-12 weeks of age and averaged 7±1 mg/d. At 20-21 weeks of age renal vascular and glomerular damage progressed as assessed histologically and urinary albumin excretion increased to 117 ± 10 mg/d in the Obese Zucker rats.

Conclusions

Obesity is a major risk factor that, along with hyperglycemia and hypertension, contributes to the progression of kidney disease. Previous studies in models of Type I diabetes have suggested that COX-2 may contribute to diabetic nephropathy. In this study researchers found increases in renal COX-2 levels and changes in TXA2 and PGE2 levels in the Obese Zucker rat. The changes in TXA2 and PGE2 are similar to those found in the diabetic patient population.

Interestingly, these changes occurred in the Obese Zucker rat at pre-hyperglycemic and pre-hypertensive stages. Renal damage was minimal at 10-12 weeks of age and progressed rapidly towards kidney failure by 20-21 weeks of age. Therefore, during the development of obesity-related diabetes, alternations in COX-2 derived metabolites could contribute to the renal damage associated with this disease. Taken as a whole, these findings suggest that COX-2 inhibitors may be beneficial for the prevention of renal damage in obesity-related type II 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.

EDITOR’S NOTE: Members of the press are invited to attend the conference and interview the researchers in person or by phone. Please contact Donna Krupa at (703) 527-7357 (office); (703) 967-2751 (cell) or djkrupa1@aol.com (email) for more information.

Meeting Dates: October 1-4, 2003
Radisson Riverfront Hotel and Convention Center, Augusta, GA


Donna Krupa | EurekAlert!
Further information:
http://www.faseb.org/aps/

More articles from Health and Medicine:

nachricht New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology

nachricht Alzheimer’s: Cellular Mechanism Provides Explanation Model for Declining Memory Performance
21.09.2016 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

Im Focus: Launch of New Industry Working Group for Process Control in Laser Material Processing

At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.

In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...

Im Focus: New laser joining technologies at ‘K 2016’ trade fair

Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.

K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

ICPE in Graz for the seventh time

20.09.2016 | Event News

Using mathematical models to understand our brain

16.09.2016 | Event News

 
Latest News

Chains of nanogold – forged with atomic precision

23.09.2016 | Life Sciences

New leukemia treatment offers hope

23.09.2016 | Health and Medicine

Self-assembled nanostructures hit their target

23.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>