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Newly identified genes influence insulin and glucose regulation
Date:1/17/2010

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 Ins 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 r
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Contact: Joan Chamberlain
NIDDKMedia@mail.nih.gov
301-496-3583
NIH/National Institute of Diabetes and Digestive and Kidney Diseases
Source:Eurekalert

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