A Family with Severe Insulin Resistance and Diabetes Due to a Mutation in AKT2-Reference-Cited by-同舟云学术

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

Published:2004-05-28 Issue:5675 Volume:304 Page:1325-1328
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

George Stella¹²³⁴⁵,Rochford Justin J.¹²³⁴⁵,Wolfrum Christian¹²³⁴⁵,Gray Sarah L.¹²³⁴⁵,Schinner Sven¹²³⁴⁵,Wilson Jenny C.¹²³⁴⁵,Soos Maria A.¹²³⁴⁵,Murgatroyd Peter R.¹²³⁴⁵,Williams Rachel M.¹²³⁴⁵,Acerini Carlo L.¹²³⁴⁵,Dunger David B.¹²³⁴⁵,Barford David¹²³⁴⁵,Umpleby A. Margot¹²³⁴⁵,Wareham Nicholas J.¹²³⁴⁵,Davies Huw Alban¹²³⁴⁵,Schafer Alan J.¹²³⁴⁵,Stoffel Markus¹²³⁴⁵,O'Rahilly Stephen¹²³⁴⁵,Barroso Inês¹²³⁴⁵

Affiliation:

1. Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.

2. Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.

3. Laboratory of Metabolic Diseases, Rockefeller University, New York, NY 10021, USA.

4. Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, UK.

5. Department of Diabetes, Endocrinology and Internal Medicine, Guy's, King's and St. Thomas' School of Medicine, London, UK.

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/PKBβ 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference20 articles.

1. The genetics of type 2 diabetes

2. Molecular diagnostics in monogenic and multifactorial forms of Type 2 diabetes

3. The PI3K–PDK1 connection: more than just a road to PKB

4. Ten years of protein kinase B signalling: a hard Akt to follow

5. Single-letter abbreviations for the amino acid residues are as follows: A Ala; C Cys; D Asp; E Glu; F Phe; G Gly; H His; I Ile; K Lys; L Leu; M Met; N Asn; P Pro; Q Gln; R Arg; S Ser; T Thr; V Val; W Trp; and Y Tyr.

Cited by 465 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Mechanism of Insulin Action;Textbook of Diabetes;2024-01-12

2. The blockade of the TGF‐β pathway alleviates abnormal glucose and lipid metabolism of lipodystrophy not obesity;Pharmacology Research & Perspectives;2024-01-04

3. Active AKT2 stimulation of SREBP1/SCD1-mediated lipid metabolism boosts hepatosteatosis and cancer;Translational Research;2024-01

4. Complex rearrangement in TBC1D4 in an individual with diabetes due to severe insulin resistance syndrome;European Journal of Human Genetics;2023-12-12

5. The pharmacological effects of Berberine and its therapeutic potential in different diseases: Role of the phosphatidylinositol 3‐kinase/AKT signaling pathway;Phytotherapy Research;2023-11-03