Featured Research

from universities, journals, and other organizations

Research Suggests How Steroids Cause Diabetes And Hypertension; Liver Plays Critical Role

Date:
July 21, 2003
Source:
Washington University School Of Medicine
Summary:
Steroids called glucocorticoids are critical for treating diseases such as asthma, arthritis and pain syndromes, but they also can trigger diabetes and hypertension. Research at Washington University School of Medicine in St. Louis now shows why these commonly used drugs have such dangerous side effects.

St. Louis, July 17, 2003 -- Steroids called glucocorticoids are critical for treating diseases such as asthma, arthritis and pain syndromes, but they also can trigger diabetes and hypertension. Research at Washington University School of Medicine in St. Louis now shows why these commonly used drugs have such dangerous side effects.

The team found that a protein called peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is critical in this process and that the liver plays a key role. The findings help explain the high incidence of diabetes and hypertension in obese individuals, a group that normally produces significantly more glucocorticoids than people of average weight.

"Glucocorticoids are very effective for treating many diseases," says first author Carlos Bernal-Mizrachi, M.D., instructor of medicine. "If we can understand the mechanisms by which these drugs cause side effects like diabetes and hypertension, we may be able to intervene and prevent these disorders in people who are taking steroids and in people who are obese."

The study appears online and in the August issue of the journal Nature Medicine. Bernal-Mizrachi led the study, in collaboration with Clay F. Semenkovich, M.D., professor of medicine and of cell biology and physiology and director of the Division of Endocrinology, Metabolism and Lipid Research, and Daniel P. Kelly, M.D., professor of medicine, of molecular biology and pharmacology and of pediatrics and director of the Center for Cardiovascular research.

Hypertension (persistent high blood pressure) and diabetes (chronic insulin deficiency) both are related to insulin-resistance, in which the body does not properly respond to insulin.

PPAR-alpha is found in the liver, kidney, muscles, blood vessels and other organs. Since it is activated by fatty acids and since glucocorticoids alter fatty acid processing, Bernal-Mizrachi and his colleagues hypothesized that the two may act together to produce the disease-causing side effects. They therefore compared mice lacking PPAR-alpha and LDLR (the receptor for low density lipoprotein, also known as "bad cholesterol") with mice lacking only LDLR.

The team found that when given the glucocorticoid dexamethasone, mice lacking only LDLR had increased levels of insulin, fasting glucose and leptin, all signs of diabetes. The animals also became less hypoglycemic when given insulin, suggesting that they were developing insulin resistance, the precursor to diabetes. Mice lacking both LDLR and PPAR-alpha showed no signs of diabetes.

Surprisingly, dexamethasone also increased blood pressure in mice that had PPAR-alpha but not LDLR; it did not have an affect on blood pressure in mice lacking both PPAR-alpha and LDLR.

"Somehow, animals missing PPAR-alpha were protected from developing diabetes and hypertension," Semenkovich says.

The team then replaced PPAR-alpha in the liver in mice lacking both PPAR-alpha and LDLR. The animals developed the same symptoms of diabetes and hypertension (high blood pressure) when chronically treated with dexamethasone as mice with normal levels of PPAR-alpha throughout the body.

The team also examined human liver cells in a petri dish. When PPAR-alpha was activated and steroids were added, expression of genes related to glucose production tripled.

"The scientific community hasn't fully appreciated the potentially important role of the liver in these conditions," Semenkovich says. "These results strongly suggest that the liver is the key to controlling blood pressure and glucose, and our preliminary evidence with human liver cells strongly suggests that the results in mice are relevant to human disease."

Next, Semenkovich, Bernal-Mizrachi and their colleagues plan to investigate the role of PPAR-alpha in healthy humans.

"We believe that diabetes, hypertension and many other disorders of western civilization are related to metabolism of fatty acids, not just glucose metabolism," Semenkovich says. "These results support that theory, because PPAR-alpha is activated by fatty acids and appears to be important in the development of these problems. Hopefully, studying this process in humans will lead to ways of preventing these potentially adverse effects of steroids and help us understand why people who get overweight have many of the symptoms of excess production of glucocorticoids."

###

Reference: Bernal-Mizrachi C, Weng S, Feng C, Finck BN, Knutsen RH, Leone TC, Coleman T, Mecham RP, Kelly DP, Semenkovich CF. Dexamethasone induction of hypertension and diabetes is PPAR-alpha dependent in LDL receptor-null mice. Nature Medicine, August, 2003.

Funding from the National Institutes of Health, the Clinical Nutrition Research Unit and the Diabetes Research and Training Center supported this research.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.


Story Source:

The above story is based on materials provided by Washington University School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School Of Medicine. "Research Suggests How Steroids Cause Diabetes And Hypertension; Liver Plays Critical Role." ScienceDaily. ScienceDaily, 21 July 2003. <www.sciencedaily.com/releases/2003/07/030721085236.htm>.
Washington University School Of Medicine. (2003, July 21). Research Suggests How Steroids Cause Diabetes And Hypertension; Liver Plays Critical Role. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2003/07/030721085236.htm
Washington University School Of Medicine. "Research Suggests How Steroids Cause Diabetes And Hypertension; Liver Plays Critical Role." ScienceDaily. www.sciencedaily.com/releases/2003/07/030721085236.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

Beatings and Addiction: Pakistan Drug 'clinic' Tortures Patients

AFP (July 24, 2014) A so-called drugs rehab 'clinic' is closed down in Pakistan after police find scores of ‘patients’ chained up alleging serial abuse. Duration 03:05 Video provided by AFP
Powered by NewsLook.com
Too Few Teens Receiving HPV Vaccination, CDC Says

Too Few Teens Receiving HPV Vaccination, CDC Says

Newsy (July 24, 2014) The Centers for Disease Control and Prevention is blaming doctors for the low number of children being vaccinated for HPV. Video provided by Newsy
Powered by NewsLook.com
New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. 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:
from the past week

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