HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/E70    most recent 00259.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Miles, P. D. Articles by Barlow, C. Search for Related Content PubMed PubMed Citation Articles by Miles, P. D. Articles by Barlow, C.

Impaired insulin secretion in a mouse model of ataxia telangiectasia

¹Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla; and ²Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California

Submitted 29 May 2006 ; accepted in final form 14 December 2006

Ataxia telangiectasia (A-T) is an autosomal recessive disease caused by mutations in the A-T mutated (ATM) gene. The gene encodes a serine/threonine kinase with important roles in the cellular response to DNA damage, including the activation of cell cycle checkpoints and induction of apoptosis. Although these functions might explain the cancer predisposition of A-T patients, the molecular mechanisms leading to glucose intolerance and diabetes mellitus (DM) are unknown. We have investigated the pathogenesis of DM in a mouse model of A-T. Here we show that young Atm-deficient mice show normal fasting glucose levels and normal insulin sensitivity. However, oral glucose tolerance testing revealed delayed insulin secretion and resulting transient hyperglycemia. Aged Atm–/– mice show a pronounced increase in blood glucose levels and a decrease in insulin and C-peptide levels. Our findings support a role for ATM in metabolic function and point toward impaired insulin secretion as the primary cause of DM in A-T.

Atm–/– mice; diabetes mellitus

This article has been cited by other articles:

				R. I. Sadreyev, J. D. Feramisco, H. Tsao, and N. V. Grishin Phenotypic categorization of genetic skin diseases reveals new relations between phenotypes, genes and pathways Bioinformatics, November 15, 2009; 25(22): 2891 - 2896. [Abstract] [Full Text] [PDF]

				I. A. Barbazetto, M. Room, N. A. Yannuzzi, G. R. Barile, J. E. Merriam, A. M. C. Bardal, K. B. Freund, L. A. Yannuzzi, and R. Allikmets ATM Gene Variants in Patients with Idiopathic Perifoveal Telangiectasia Invest. Ophthalmol. Vis. Sci., September 1, 2008; 49(9): 3806 - 3811. [Abstract] [Full Text] [PDF]