Featured Research

from universities, journals, and other organizations

Scientists Link Energy Metabolism And Fertility

September 22, 2000
Howard Hughes Medical Institute
Scientists have discovered that a protein that translates insulin signals during carbohydrate metabolism also plays an important role in female reproduction and in the regulation of appetite and obesity in mice.

September 21, 2000 — Scientists have discovered that a protein that translates insulin signals during carbohydrate metabolism also plays an important role in female reproduction and in the regulation of appetite and obesity in mice.

Related Articles

According to the researchers, the link between energy metabolism and fertility may underlie an evolutionarily conserved pathway that makes humans and animals fit for reproduction. Further study of the insulin receptor substrate-2 (IRS-2) protein may offer alternative avenues for the treatment of diabetes and infertility.

In an article published in the September 21, 2000, issue of the journal Nature, Howard Hughes Medical Institute investigator Morris F. White and colleagues at Harvard Medical School report that female mice that lack IRS-2 show severely impaired reproduction. Mice lacking IRS-2 have defective ovaries that prevent egg release and they show abnormal production of the egg-releasing hormone from the pituitary gland.

The IRS family of proteins mediates the transmission of the insulin signal to proteins in other tissues. The IRS proteins were discovered in White's laboratory at Harvard's Joslin Diabetes Center. "In earlier experiments in which we knocked out IRS-2 in mice, we realized that it had broad effects on the neuroendocrine system," White said. "Male IRS-2 knockout mice became diabetic within ten weeks, not just because their tissues were insulin-resistant, but because IRS-2 also played a major role in keeping beta cells in the pancreas alive to secrete insulin, compensating for the insulin resistance."

IRS-2-knockout mice mimic non-insulin-dependent diabetes, or type 2 diabetes, which accounts for more than 90 percent of the cases of human diabetes. "One of the most striking results in these knockouts was that the female mice don't develop diabetes until about 20 weeks after birth, whereas the males get diabetes at 10 weeks," said White.

Thus, when postdoctoral fellow Deborah Burks, lead author of the Nature paper, decided to examine fertility in the mice, she began with the female mice since they remained healthy longer. "One of the first things she found was that these mice overeat and gain weight, effects not observable in the males because when their diabetes kicks in, they begin to waste away," said White. "However, it wasn't until she tried to breed the females that she found they were terrible breeders. We realized that these female mice were infertile," he said. "So, what we thought was an uninformative animal turned out to be highly informative."

Detailed physiological studies of the females showed that their ovaries had few mature egg-containing structures called follicles and there was no production of luteinizing hormone that triggers egg release. Additional studies showed that the animals' brains were resistant to the appetite-regulating hormone leptin, causing the animals to overeat and become obese.

"So, if these findings in mice extend to people, it looks as if the IRS-2 branch of the insulin-signaling system promotes a lot of processes that improve our fitness for reproduction," White says. "It controls our food intake, makes us more fertile and allows our beta cells to survive to secrete insulin that keeps carbohydrates and insulin gene expression under control. IRS-2 coordinates reproduction, feeding behavior, and internal carbohydrate homeostasis, which is critical since pregnancy and reproduction is a very energy-intensive process," he said.

Earlier studies by other research teams showed that a similar linkage of reproduction and energy metabolism exists in the roundworm C. elegans and in the fruit fly Drosophila, suggesting that this theme is conserved throughout the animal kingdom, said White.

The discovery of IRS-2's coordinating role suggests that insulin resistance might be an underlying trigger of obesity in diabetics, said White. "Insulin resistance may disrupt the leptin set point," he said. "The person starts to eat more and gain weight, and that elevated weight causes an additional layer of insulin resistance that causes the weight to mushroom out of control."

The key role of IRS-2 highlights the importance of developing anti-diabetes drugs that enhance IRS-2 activity, he said. Also, he said, the finding hints that IRS-2 malfunctions may be at the root of polycystic ovarian syndrome (PCOS). Women with PCOS have a range of problems, including infertility, obesity and insulin-resistance. "While the role of IRS-2 in these areas is currently speculative, we will try to understand in detail how IRS-2 regulates the ovaries to promote fertility. We will also be looking at IRS-2 function in the brain and other tissues," said White.

Story Source:

The above story is based on materials provided by Howard Hughes Medical Institute. Note: Materials may be edited for content and length.

Cite This Page:

Howard Hughes Medical Institute. "Scientists Link Energy Metabolism And Fertility." ScienceDaily. ScienceDaily, 22 September 2000. <www.sciencedaily.com/releases/2000/09/000922072356.htm>.
Howard Hughes Medical Institute. (2000, September 22). Scientists Link Energy Metabolism And Fertility. ScienceDaily. Retrieved January 25, 2015 from www.sciencedaily.com/releases/2000/09/000922072356.htm
Howard Hughes Medical Institute. "Scientists Link Energy Metabolism And Fertility." ScienceDaily. www.sciencedaily.com/releases/2000/09/000922072356.htm (accessed January 25, 2015).

Share This

More From ScienceDaily

More Health & Medicine News

Sunday, January 25, 2015

Featured Research

from universities, journals, and other organizations

Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Mistakes Should Serve a Lesson Says WHO

Ebola Mistakes Should Serve a Lesson Says WHO

AFP (Jan. 25, 2015) The World Health Organization&apos;s chief on Sunday admitted the UN agency had been caught napping on Ebola, saying it should serve a lesson to avoid similar mistakes in future. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Disneyland Measles Outbreak Spreads To 5 States

Disneyland Measles Outbreak Spreads To 5 States

Newsy (Jan. 24, 2015) Much of the Disneyland measles outbreak is being blamed on the anti-vaccination movement. The CDC encourages just about everyone get immunized. Video provided by Newsy
Powered by NewsLook.com
Growing Measles Outbreak Worries Calif. Parents

Growing Measles Outbreak Worries Calif. Parents

AP (Jan. 23, 2015) Public health officials are rushing to contain a measles outbreak that has sickened 70 people across 6 states and Mexico. The AP&apos;s Raquel Maria Dillon has more. (Jan. 23) Video provided by AP
Powered by NewsLook.com
Smart Wristband to Shock Away Bad Habits

Smart Wristband to Shock Away Bad Habits

Reuters - Innovations Video Online (Jan. 23, 2015) A Boston start-up is developing a wristband they say will help users break bad habits by jolting them with an electric shock. Ben Gruber reports. Video provided by Reuters
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.


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


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