Featured Research

from universities, journals, and other organizations

One injection stops diabetes in its tracks: Treatment reverses symptoms of type 2 diabetes in mice without side effects

Date:
July 16, 2014
Source:
Salk Institute for Biological Studies
Summary:
In mice with diet-induced diabetes -- the equivalent of type 2 diabetes in humans -- a single injection of the protein FGF1 is enough to restore blood sugar levels to a healthy range for more than two days. The discovery could lead to a new generation of safer, more effective diabetes drugs. The team found that sustained treatment with the protein doesn't merely keep blood sugar under control, but also reverses insulin insensitivity, the underlying physiological cause of diabetes. Equally exciting, the newly developed treatment doesn't result in side effects common to most current diabetes treatments.

In the liver tissue of obese animals with type 2 diabetes, unhealthy, fat-filled cells are prolific (small white cells, panel A). After chronic treatment through FGF1 injections, the liver cells successfully lose fat and absorb sugar from the bloodstream (small purple cells, panel B) and more closely resemble cells of normal, non-diabetic animals.
Credit: Courtesy of the Salk Institute for Biological Studies

In mice with diet-induced diabetes -- the equivalent of type 2 diabetes in humans -- a single injection of the protein FGF1 is enough to restore blood sugar levels to a healthy range for more than two days. The discovery by Salk scientists, published today in the journal Nature, could lead to a new generation of safer, more effective diabetes drugs.

The team found that sustained treatment with the protein doesn't merely keep blood sugar under control, but also reverses insulin insensitivity, the underlying physiological cause of diabetes. Equally exciting, the newly developed treatment doesn't result in side effects common to most current diabetes treatments.

"Controlling glucose is a dominant problem in our society," says Ronald M. Evans, director of Salk's Gene Expression Laboratory and corresponding author of the paper. "And FGF1 offers a new method to control glucose in a powerful and unexpected way."

Type 2 diabetes, which can be brought on by excess weight and inactivity, has skyrocketed over the past few decades in the United States and around the world. Almost 30 million Americans are estimated to have the disease, where glucose builds up in the bloodstream because not enough sugar-carting insulin is produced or because cells have become insulin-resistant, ignoring signals to absorb sugar. As a chronic disease, diabetes can cause serious health problems and has no specific cure. Rather it is managed -- with varying levels of success -- through a combination of diet, exercise and pharmaceuticals.

Diabetes drugs currently on the market aim to boost insulin levels and reverse insulin resistance by changing expression levels of genes to lower glucose levels in the blood. But drugs, such as Byetta, which increase the body's production of insulin, can cause glucose levels to dip too low and lead to life-threatening hypoglycemia, as well as other side effects.

In 2012, Evans and his colleagues discovered that a long-ignored growth factor had a hidden function: it helps the body respond to insulin. Unexpectedly, mice lacking the growth factor, called FGF1, quickly develop diabetes when placed on a high-fat diet, a finding suggesting that FGF1 played a key role in managing blood glucose levels. This led the researchers to wonder whether providing extra FGF1 to diabetic mice could affect symptoms of the disease.

Evans' team injected doses of FGF1 into obese mice with diabetes to assess the protein's potential impact on metabolism. Researchers were stunned by what happened: they found that with a single dose, blood sugar levels quickly dropped to normal levels in all the diabetic mice.

"Many previous studies that injected FGF1 showed no effect on healthy mice," says Michael Downes, a senior staff scientist and co-corresponding author of the new work. "However, when we injected it into a diabetic mouse, we saw a dramatic improvement in glucose."

The researchers found that the FGF1 treatment had a number of advantages over the diabetes drug Actos, which is associated with side effects ranging from unwanted weight gain to dangerous heart and liver problems. Importantly, FGF1 -- even at high doses -- did not trigger these side effects or cause glucose levels to drop to dangerously low levels, a risk factor associated with many glucose-lowering agents. Instead, the injections restored the body's own ability to naturally regulate insulin and blood sugar levels, keeping glucose amounts within a safe range -- effectively reversing the core symptoms of diabetes.

"With FGF1, we really haven't seen hypoglycemia or other common side effects," says Salk postdoctoral research fellow Jae Myoung Suh, a member of Evans' lab and first author of the new paper. "It may be that FGF1 leads to a more 'normal' type of response compared to other drugs because it metabolizes quickly in the body and targets certain cell types."

The mechanism of FGF1 still isn't fully understood -- nor is the mechanism of insulin resistance -- but Evans' group discovered that the protein's ability to stimulate growth is independent of its effect on glucose, bringing the protein a step closer to therapeutic use.

"There are many questions that emerge from this work and the avenues for investigating FGF1 in diabetes and metabolism are now wide open," Evans says. Pinning down the signaling pathways and receptors that FGF1 interacts with is one of the first questions he'd like to address. He's also planning human trials of FGF1 with collaborators, but it will take time to fine-tune the protein into a therapeutic drug.

"We want to move this to people by developing a new generation of FGF1 variants that solely affect glucose and not cell growth," he says. "If we can find the perfect variation, I think we will have on our hands a very new, very effective tool for glucose control."

Other researchers on the study were Maryam Ahmadian, Eiji Yoshihara, Weiwei Fan, Yun-Qiang Yin, Ruth T. Yu, and Annette R. Atkins of the Salk Institute for Biological Studies; Weilin Liu, Johan W. Jonker, Theo van Dijk, and Rick Havinga of the University of Groningen; Christopher Liddle of the University of Sydney; Denise Lackey, Olivia Osborn, and Jerrold M. Olefsky of the University of California at San Diego; and Regina Goetz, Zhifeng Huang, and Moosa Mohammadi of the New York University School of Medicine.

Ronald Evans is a Howard Hughes Medical Institute investigator and is also supported by grants from the National Institutes of Health, the Leona M. and Harry B. Helmsley Charitable Trust, the Glenn Foundation for Medical Research, Ipsen/Biomeasure, CIRM, and the Ellison Medical Foundation. Other study authors received grants from the National Institutes of Health, the Australian National Health and Medical Research Council, the European Research Council, the Human Frontier Science Program, the Netherlands Organisation for Scientific Research, and the Dutch Digestive Foundation.


Story Source:

The above story is based on materials provided by Salk Institute for Biological Studies. Note: Materials may be edited for content and length.


Journal Reference:

  1. Jae Myoung Suh, Johan W. Jonker, Maryam Ahmadian, Regina Goetz, Denise Lackey, Olivia Osborn, Zhifeng Huang, Weilin Liu, Eiji Yoshihara, Theo H. van Dijk, Rick Havinga, Weiwei Fan, Yun-Qiang Yin, Ruth T. Yu, Christopher Liddle, Annette R. Atkins, Jerrold M. Olefsky, Moosa Mohammadi, Michael Downes, Ronald M. Evans. Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer. Nature, 2014; DOI: 10.1038/nature13540

Cite This Page:

Salk Institute for Biological Studies. "One injection stops diabetes in its tracks: Treatment reverses symptoms of type 2 diabetes in mice without side effects." ScienceDaily. ScienceDaily, 16 July 2014. <www.sciencedaily.com/releases/2014/07/140716131541.htm>.
Salk Institute for Biological Studies. (2014, July 16). One injection stops diabetes in its tracks: Treatment reverses symptoms of type 2 diabetes in mice without side effects. ScienceDaily. Retrieved October 2, 2014 from www.sciencedaily.com/releases/2014/07/140716131541.htm
Salk Institute for Biological Studies. "One injection stops diabetes in its tracks: Treatment reverses symptoms of type 2 diabetes in mice without side effects." ScienceDaily. www.sciencedaily.com/releases/2014/07/140716131541.htm (accessed October 2, 2014).

Share This



More Health & Medicine News

Thursday, October 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pregnancy Spacing Could Have Big Impact On Autism Risks

Pregnancy Spacing Could Have Big Impact On Autism Risks

Newsy (Oct. 1, 2014) A new study says children born less than one year and more than five years after a sibling can have an increased risk for autism. Video provided by Newsy
Powered by NewsLook.com
Ebola Patient Told Hospital He Was from Liberia

Ebola Patient Told Hospital He Was from Liberia

AP (Oct. 1, 2014) The first Ebola patient diagnosed in the U.S. initially went to a Dallas emergency room last week but was sent home, despite telling a nurse that he had been in disease-ravaged West Africa, the hospital acknowledged Wednesday. (Oct. 1) Video provided by AP
Powered by NewsLook.com
Robotic Hair Restoration

Robotic Hair Restoration

Ivanhoe (Oct. 1, 2014) A new robotic procedure is changing the way we transplant hair. The ARTAS robot leaves no linear scarring and provides more natural results. Video provided by Ivanhoe
Powered by NewsLook.com
Insertable Cardiac Monitor

Insertable Cardiac Monitor

Ivanhoe (Oct. 1, 2014) A heart monitor the size of a paperclip that can save your life. The “Reveal Linq” allows a doctor to monitor patients with A-Fib on a continuous basis for up to 3 years! Video provided by Ivanhoe
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