Newly identified genes influence insulin and glucose regulation

This press release is an announcement submitted by NIH/National Institute of Diabetes and Digestive and Kidney Diseases, and was not written by Diabetes Health.

The discovery highlights the role of incretin hormones, which are released from endocrine cells in the gut.

Jan 23, 2010

An international research consortium has found 13 new genetic variants that influence blood glucose regulation, insulin resistance, and the function of insulin-secreting beta cells in populations of European descent. Five of the newly discovered variants increase the risk of developing type 2 diabetes, the most common form of diabetes.

The results of two studies, conducted by the Meta-Analyses of Glucose and Insulin Related Traits Consortium (MAGIC), provide important clues about the role of beta cells in the development of type 2 diabetes. The studies, funded in part by the National Institutes of Health, appear online Jan. 17, 2010, in Nature Genetics.

"The findings from these ambitious, large-scale studies represent an enormous achievement in international cooperation involving hundreds of researchers and many thousands of individuals who contributed genetic samples for the study. The results give us exciting new directions for future research in the biology of type 2 diabetes, which poses a major and growing public health problem worldwide," said NIH Director Francis S. Collins, M.D., Ph.D., an author of both papers.

In one paper, the MAGIC investigators set out to find genes that influence metabolic traits, including fasting glucose and insulin levels and measures of beta cell function and insulin resistance. About 2.5 million genetic variants were analyzed in 21 genome-wide association studies (GWAS) that had enrolled 46,186 individuals who did not have diabetes and had been tested for measures of glucose and insulin regulation. GWAS look for common genetic associations by scanning the DNA of thousands of individuals. The huge numbers of genetic samples boosts the chances of finding subtle associations of genetic variants with specific diseases or traits. The most common variation is a change in a single nucleotide polymorphism (SNP), or single base pair change, in one of the building blocks of DNA.

The initial analysis yielded 25 candidate SNPs that were further tested in genetic samples from about 77,000 additional individuals. This step led to 16 SNPs that were clearly associated with fasting glucose and beta cell function and two SNPs associated with fasting insulin and insulin resistance. The investigators then asked whether any of the SNPs raise type 2 diabetes risk by comparing gene variants from thousands of people with and without type 2 diabetes.

Among the five variants that raise type 2 diabetes risk, one of the more intriguing SNPs is in the region of ADCY5, which influences fasting and postprandial glucose levels. Another is in FADS1, which is linked with fasting glucose as well as lipid traits. None of the variants found in the MAGIC studies were associated with type 1 diabetes, an autoimmune disease that has been traced mainly to genes that regulate immune function.

"The hallmarks of type 2 diabetes are insulin resistance and impaired beta cell function. We were intrigued to find that most of the newly found variants influence insulin secretion rather than insulin resistance. Only one variant, near IGF1, is associated with insulin resistance," said lead author Inês Barroso, Ph.D., of the Wellcome Trust Sanger Institute, Cambridge, England.

Beta cell impairment may play a larger role in type 2 diabetes than previously recognized, the authors suggest. Also, the environment may contribute to insulin resistance more than it does to insulin secretion. Learning how the genes influence cell signaling and development, glucose sensing, and hormonal regulation will assist the development of targeted methods to prevent and treat diabetes, they conclude.

"Our study shows that genetic studies of glycemic traits can identify loci for type 2 diabetes risk," says lead co-author Jose Florez, M.D., Ph.D., of Massachusetts General Hospital and Harvard Medical School. "However, not all loci that influence blood glucose regulation are associated with greater risk for type 2 diabetes. Some loci elevate fasting glucose slightly but do not raise diabetes risk. It appears that it's not the mere elevation in glucose, but how glucose is raised, that determines type 2 diabetes risk."

In the second paper, MAGIC researchers evaluated genetic associations with glucose levels 2 hours after an oral glucose challenge in a subset of 15,234 participants. They found that a genetic variant in the gene GIPR, which codes for the receptor of gastric inhibitory polypeptide, a beta cell regulating hormone, influences blood glucose levels after a glucose challenge, or sugary meal. Individuals with the risk variant have reduced beta cell function.

The discovery highlights the role of incretin hormones, which are released from endocrine cells in the gut. "This finding adds to a growing body of evidence implicating the incretin pathways in type 2 diabetes risk. These pathways, which stimulate insulin secretion in response to digestion of food, may offer a potential avenue for therapeutic intervention," said senior author Richard Watanabe, Ph.D., of the University of Southern California.

The variants were found in populations of European descent, but the researchers expect that some will have similar effects in other populations. Future research will attempt to answer that question. "Even with the discovery of these variants, we've only explained about 10 percent of the genetic contribution to fasting glucose in people who do not have diabetes," Florez cautioned. Yet undiscovered genes may be found by studies that increase sample sizes to detect smaller effects and look for less common variants as well as non-SNP variants-for example, insertions, deletions, and duplications of DNA that haven't been well studied yet.

* * *

Source:

http://www.eurekalert.org/pub_releases/2010-01/niod-nig011410.php

NIH/National Institute of Diabetes and Digestive and Kidney Diseases

Click Here To View Or Post Comments

Categories: Beta Cells, Blood Glucose, Diabetes, Diabetes, Food, Insulin, Research, Type 1 Issues, Type 2 Issues


Take the Diabetes Health Pump Survey
See What's Inside
Read this FREE issue now
For healthcare professionals only
  • What's on the Horizon with Diabetes Research and Therapy
See the entire table of contents here!

You can view the current or previous issues of Diabetes Health online, in their entirety, anytime you want.
Click Here To View

See if you qualify for our free healthcare professional magazines. Click here to start your application for Pre-Diabetes Health, Diabetes Health Pharmacist and Diabetes Health Professional.

Learn More About the Professional Subscription

Free Diabetes Health e-Newsletter

Latest
Popular
Top Rated
Print | Email | Share | Comments (2)

You May Also Be Interested In...


Comments

Posted by Colleen Fuller on 24 January 2010

This is all very interesting. Unfortunately, it isn't a significant contribution to what we know about how to prevent Type 2 diabetes. What we need are meaningful studies that look at strategies to reduce poverty, a significant trigger about which we can do something. I am fed up with the Pharma-directed research that steers us further and further away from non-pharmaceutical interventions like good public policy to ensure wealth is distributed more fairly.

Posted by cde on 25 January 2010

The photo used to illustrate injection of insulin (for this article) does not indicate the correct position of the syringe when making the injection.

Dr. Stan De Loach
Certified Diabetes Educator
México, D. F.


Add your comments about this article below. You can add comments as a registered user or anonymously. If you choose to post anonymously your comments will be sent to our moderator for approval before they appear on this page. If you choose to post as a registered user your comments will appear instantly.

When voicing your views via the comment feature, please respect the Diabetes Health community by refraining from comments that could be considered offensive to other people. Diabetes Health reserves the right to remove comments when necessary to maintain the cordial voice of the diabetes community.

For your privacy and protection, we ask that you do not include personal details such as address or telephone number in any comments posted.

Don't have your Diabetes Health Username? Register now and add your comments to all our content.

Have Your Say...


Username: Password:
Comment:
©1991-2014 Diabetes Health | Home | Privacy | Press | Advertising | Help | Contact Us | Donate | Sitemap

Diabetes Health Medical Disclaimer

The information on this site is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment. All content, including text, graphics, images, and information, contained on or available through this website is for general information purposes only. Opinions expressed here are the opinions of writers, contributors, and commentators, and are not necessarily those of Diabetes Health. Never disregard professional medical advice or delay seeking medical treatment because of something you have read on or accessed through this website.