A Family with Severe Insulin Resistance and Diabetes Due to a Mutation in AKT2

Overview

Journal Science

Specialty Science

Date 2004 May 29

PMID 15166380

Citations 228

Authors

Stella George

Justin J Rochford

Christian Wolfrum

Sarah L Gray

Sven Schinner

Jenny C Wilson

Maria A Soos

Peter R Murgatroyd

Rachel M Williams

Carlo L Acerini

David B Dunger

David Barford

A Margot Umpleby

Nicholas J Wareham

Huw Alban Davies

Alan J Schafer

Markus Stoffel

Stephen ORahilly

Ines Barroso

Affiliations

Soon will be listed here.

Abstract

Inherited defects in signaling pathways downstream of the insulin receptor have long been suggested to contribute to human type 2 diabetes mellitus. Here we describe a mutation in the gene encoding the protein kinase AKT2/PKBbeta in a family that shows autosomal dominant inheritance of severe insulin resistance and diabetes mellitus. Expression of the mutant kinase in cultured cells disrupted insulin signaling to metabolic end points and inhibited the function of coexpressed, wild-type AKT. These findings demonstrate the central importance of AKT signaling to insulin sensitivity in humans.

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