NEW YORK (Reuters Health) - A missense mutation in the serine/threonine kinase gene (AKT2) has been identified in a family with autosomal dominant inheritance of severe insulin resistance and type 2 diabetes, investigators report in the May 28th issue of Science.
Dr. Stephen O’Rahilly, at the University of Cambridge in the UK, and colleagues screened genomic DNA from 104 unrelated subjects with severe insulin resistance. They identified a heterozygous R-to-H substitution at amino acid 274 of AKT2 in a lipodystrophic 34-year old nonobese woman who developed diabetes mellitus at age 30.
She and three maternal relatives with the same mutated allele were severely hyperinsulinemic. Two of the three relatives had developed diabetes while in their late 30s. The mutation was not found in three other clinically normal first-degree relatives or in 1500 Caucasian control subjects.
An animal model showed that this mutation decreases lipid accumulation in preadipocytes and impairs adipogenesis. Consistent with this observation, the proband, who had severe insulin resistance in both the liver and peripheral tissues, had a 35% lower body fat composition compared with other women of similar BMI.
“These findings demonstrate the central importance of AKT signaling to insulin sensitivity in humans,” the authors write, which should lead to “important clues to understanding more common forms” of diabetes.
Source: Science 2004;304:1325-1328. [ Google search on this article ]
MeSH Headings:Lipodystrophy: Skin Diseases, Metabolic: Protein-Serine-Threonine Kinases: Mutation, MissenseCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
