Featured Research

from universities, journals, and other organizations

Hope For Significant New Diabetes Treatment In Stanford Discovery

Date:
September 24, 2006
Source:
Stanford University Medical Center
Summary:
Certain immune-suppressing drugs, such as those taken by patients who have had organ transplants, greatly increase the risk of developing diabetes. Researcher Seung Kim has discovered that the protein calcineurin plays a key role in the health of certain insulin-producing cells in the pancreas.

Certain immune-suppressing drugs, such as those taken by patients who have had organ transplants, greatly increase the risk of developing diabetes. These drugs are known to put a stranglehold on a protein called calcineurin.

Related Articles


So it's not exactly a surprise that Seung Kim, MD, PhD, assistant professor of developmental biology at the Stanford University School of Medicine, chose to study why calcineurin inhibition leads to the disease. What is surprising is just how central calcineurin turns out to be in the health and happiness of the insulin-producing pancreatic beta cells. His findings, to be published in the Sept. 21 issue of Nature, could shake up diabetes research, lead to new classes of diabetes drugs and aid in efforts to develop stem cell treatments for diabetes.

"This work has the potential to be big," said Scott Campbell, PhD, vice president of research for the American Diabetes Association. He said that drugs based on this research could potentially expand the numbers of the few beta cells that remain in diabetics and make those cells perform better. "That would have a major impact on the lives of people with diabetes."

In diabetes, the beta cells produce too little insulin or none at all, which prevents cells of the body from being able to take in sugar after a meal. Sugar accumulates in the blood, damaging the blood vessels, kidneys and eyes. Diabetics are also prone to nerve damage. In the United States, 20.8 million people, or 7 percent of the population, have diabetes.

Knowing the potential link between calcineurin-inhibiting drugs and diabetes, Kim and MD/PhD graduate student Jeremy Heit collaborated with Gerald Crabtree, MD, professor of pathology, in a series of experiments to clarify the connection. They worked with mice that had been bred to produce calcineurin in the pancreas only until they were born. After birth, the pancreas in each mouse stopped producing the protein. By 12 weeks of age, the mice, which had been born with a normal number of beta cells, were severely diabetic.

Squelching calcineurin prevented the beta cells from increasing their numbers as the mice grew - more body mass requires more beta cells to keep blood sugar in check. It also reduced the amount of insulin made by the existing beta cells. What's more, calcineurin was found to regulate 10 genes that already had been associated with diabetes.

"This work has led us and others to think in entirely new ways about diabetes," Heit said. Until now people had identified individual genes or processes that were involved in diabetes. The new findings show that these lines of research are connected through a common regulator in calcineurin.

Heit and Kim used further genetic trickery to bypass calcineurin by artificially activating its protein sidekick, called NFAT. Beta cells lacking calcineurin but with active NFAT behaved normally, multiplying as the mice aged and producing normal amounts of insulin.

The implications of these findings are many:

  • Drugs that enhance the activity of calcineurin or NFAT could become a new treatment for type-2, or adult-onset diabetes, in which the beta cells don't produce enough insulin.
  • Drugs that inhibit calcineurin or NFAT could treat diseases in which the beta cells produce too much insulin, such as hypoglycemia or some pancreatic tumors.
  • Treating isolated beta cells with drugs that enhance calcineurin could make those cells divide, producing more cells for transplantation.
  • Activating calcineurin could help Kim in his efforts to direct embryonic stem cells to become insulin-producing cells.

Kim, whose work in diabetes includes the development of islet cells, identifying new drug targets and potential stem cell treatments, said the calcineurin findings have wide-ranging implications. "The finding that the calcineurin pathway regulates other pathways in the beta cell makes it highly relevant to many areas of diabetes research," he said.

Campbell said the next step is to verify that the findings in mice also hold true in humans. "This is a step in the right direction and a major leap forward, but now we need to take it into to humans," he said.

Other Stanford researchers who participated in this work include postdoctoral fellow Asa Apelqvist. PhD; graduate students Monte Winslow and Joel Neilson, and research assistant Xueying Gu.

Heit is the recipient of an American Diabetes Association Medical Scholars Grant. Winslow is supported by a Stanford graduate fellowship and a Howard Hughes Medical Institute Predoctoral Fellowship. The study was supported by awards to Crabtree from HHMI and the NIH, and to Kim from the NIH, the Biomedical Scholars Program of the Pew Charitable Trusts and the Stephen and Caroline Kaufer Fund for Neuroendocrine Tumor Research.


Story Source:

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


Cite This Page:

Stanford University Medical Center. "Hope For Significant New Diabetes Treatment In Stanford Discovery." ScienceDaily. ScienceDaily, 24 September 2006. <www.sciencedaily.com/releases/2006/09/060920193541.htm>.
Stanford University Medical Center. (2006, September 24). Hope For Significant New Diabetes Treatment In Stanford Discovery. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2006/09/060920193541.htm
Stanford University Medical Center. "Hope For Significant New Diabetes Treatment In Stanford Discovery." ScienceDaily. www.sciencedaily.com/releases/2006/09/060920193541.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. 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