Featured Research

from universities, journals, and other organizations

Scientists unravel brain-hormone circuit that helps police diabetes, female fertility

Date:
April 8, 2010
Source:
UT Southwestern Medical Center
Summary:
New findings suggest that the hormones leptin and insulin work together in specific neurons in the hypothalamus region of the brain to affect both the regulation of blood sugar levels in the body and, surprisingly, female fertility.

New findings by UT Southwestern Medical Center researchers suggest that the hormones leptin and insulin work together in specific neurons in the hypothalamus region of the brain to affect both the regulation of blood sugar levels in the body and, surprisingly, female fertility.

"Many people, and even many physicians, think you develop diabetes that is solely secondary to obesity," said Dr. Joel Elmquist, professor of internal medicine and pharmacology at UT Southwestern and senior author of the study, which appears online and in the current issue of Cell Metabolism. "Our findings indicate that is not necessarily the case, at least in mice. We can make the animals very diabetic without obesity, suggesting that there may be a circuit or path of resistance to these signals in the brain that helps explain the powerful anti-diabetic actions of leptin."

Additionally, the study indicates that a person may not have to be obese to develop type 2 diabetes, Dr. Elmquist added.

Prior research by Dr. Roger Unger, professor of internal medicine at UT Southwestern, has shown that a single injection of leptin, a hormone produced by the body's fat cells, can restore terminally ill rodents with type 1 diabetes to full health. The underlying cellular mechanisms that caused that effect, however, have been elusive.

Although diabetes and obesity often go hand in hand, Dr. Elmquist said the new findings indicate that a group of brain cells called pro-opiomelanocortin, or POMC, neurons help regulate glucose and insulin independent of food intake and body weight. POMC neurons, found in the hypothalamus, a small region of the brain, previously have been shown to play an important role in suppressing appetite and inducing weight loss.

In the current study, the researchers genetically engineered mice to lack both leptin and insulin receptors in their POMC neurons. Both receptors remained intact in all other cell types and tissues, including the liver and ovaries.

Prior research has shown that deleting the leptin receptor alone from POMC neurons results in mild obesity and has little effect on the regulation of blood sugar levels, while deleting only the insulin receptor has no noticeable impact on body weight or blood sugar regulation.

The researchers found, however, that when they removed both receptors from these particular neurons the mice displayed systemic insulin resistance and became severely diabetic but not obese. Dr. Elmquist said the findings suggest that leptin and insulin -- when acting on these neurons in the brain -- are both necessary and can compensate for each other if there's a shortage of one.

"There seems to be what I call a functional redundancy in these neurons as it relates to blood sugar regulation," said Dr. Elmquist. "We don't know if the same neurons respond to both leptin and insulin, but it is clear that functionally leptin can compensate for a lack of insulin and vice versa."

The researchers also found that female mice that lacked the hormone receptors in POMC neurons had difficulty reproducing and produced smaller litters than mice lacking just one of the receptors. This is due in part to the fact that the females lacking both receptors had extremely high levels of androgens, the researchers speculate. The most well-known androgen is the male sex hormone testosterone.

"Reproductive endocrinology isn't my area of expertise, but these findings were nonetheless completely unexpected," Dr. Elmquist said. "We believe this may be one of the first genetic models of polycystic ovary syndrome."

Polycystic ovary syndrome, or PCOS, is a metabolic disorder characterized by abnormal hormone levels. It is often associated with a wide range of afflictions in women, ranging from obesity and excessive facial hair to more severe disorders, such as infertility, diabetes and heart disease.

Dr. Elmquist said one of his goals is to understand better how these hypothalamic POMC neurons control glucose production in the liver.

The study is also part of UT Southwestern's Task Force for Obesity Research. In 2007, the multidisciplinary group received a $22 million grant from the National Institutes of Health to enhance its efforts to attack obesity from every angle. The award is one of nine interdisciplinary research consortia sponsored by the NIH Roadmap for Medical Research, a series of initiatives designed to transform the nation's medical research capabilities. The UT Southwestern group is the only one focused on obesity.

Other UT Southwestern researchers involved in the study were Drs. Carol Elias and Roberto Coppari, assistant professors of internal medicine; Dr. Jeffrey Zigman, assistant professor of internal medicine and psychiatry; Drs. Makoto Fukuda and Yong Xu, instructors of internal medicine; Dr. Kevin Williams, assistant instructor of internal medicine; Drs. Eric Berglund, William Holland and Jen-Chieh Chuang, postdoctoral research fellows in internal medicine; Danielle Lauzon, research assistant; Charlotte Lee, senior research scientist; Dr. James Richardson, professor of pathology, molecular biology and plastic surgery; Dr. Philipp Scherer, professor of internal medicine and cell biology; Dr. Jennifer Hill, lead author and former instructor of internal medicine; Dr. You-Ree Cho, former postdoctoral research fellow in internal medicine; and Michelle Choi, former research assistant in internal medicine. Researchers from the Albert Einstein College of Medicine, Beth Israel Deaconess Medical Center and the University of Cologne in Germany, also contributed to the work.

The study was funded by the American Diabetes Association, the Richard and Susan Smith Family Foundation, the NIH and DFG, a German research foundation.


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Hill et al. Direct Insulin and Leptin Action on Pro-opiomelanocortin Neurons Is Required for Normal Glucose Homeostasis and Fertility. Cell Metabolism, 2010; DOI: 10.1016/j.cmet.2010.03.002

Cite This Page:

UT Southwestern Medical Center. "Scientists unravel brain-hormone circuit that helps police diabetes, female fertility." ScienceDaily. ScienceDaily, 8 April 2010. <www.sciencedaily.com/releases/2010/04/100406125538.htm>.
UT Southwestern Medical Center. (2010, April 8). Scientists unravel brain-hormone circuit that helps police diabetes, female fertility. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2010/04/100406125538.htm
UT Southwestern Medical Center. "Scientists unravel brain-hormone circuit that helps police diabetes, female fertility." ScienceDaily. www.sciencedaily.com/releases/2010/04/100406125538.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Costs Keep Mounting

Ebola Costs Keep Mounting

Reuters - Business Video Online (Sep. 23, 2014) The WHO has warned up to 20,000 people could be infected with Ebola over the next few weeks. As Sonia Legg reports, the implications for the West African countries suffering from the disease are huge. Video provided by Reuters
Powered by NewsLook.com
Ebola Cases Could Reach 1.4 Million Within 4 Months

Ebola Cases Could Reach 1.4 Million Within 4 Months

Newsy (Sep. 23, 2014) Health officials warn that without further intervention, the number of Ebola cases in Liberia and Sierra Leone could reach 1.4 million by January. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Cases to Triple in Weeks Without Drastic Action

WHO: Ebola Cases to Triple in Weeks Without Drastic Action

AFP (Sep. 23, 2014) The number of Ebola infections will triple to 20,000 by November, soaring by thousands every week if efforts to stop the outbreak are not stepped up radically, the WHO warned in a study on Tuesday. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
5 Ways Men Can Prevent Most Heart Attacks

5 Ways Men Can Prevent Most Heart Attacks

Newsy (Sep. 23, 2014) No surprise here: A recent study says men can reduce their risk of heart attack by maintaining a healthy lifestyle, which includes daily exercise. 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