A family with severe insulin resistance and diabetes due to a mutation in AKT2

S George; J J Rochford; C Wolfrum; S L Gray; S Schinner; J C Wilson; M A Soos; P R Murgatroyd; R M Williams; C L Acerini; D B Dunger; D Barford; A M Umpleby; N J Wareham; H A Davies; A J Schafer; M Stoffel; S O'Rahilly; I Barroso

doi:10.1126/science.1096706

A family with severe insulin resistance and diabetes due to a mutation in AKT2

S George, J J Rochford, C Wolfrum, S L Gray, S Schinner, J C Wilson, M A Soos, P R Murgatroyd, R M Williams, C L Acerini, D B Dunger, D Barford, A M Umpleby, N J Wareham, H A Davies, A J Schafer, M Stoffel, S O'Rahilly, I Barroso

King's College London

Research output: Contribution to journal › Article › peer-review

469 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1325 - 1328
Number of pages	4
Journal	Science
Volume	304
Issue number	5675
DOIs	https://doi.org/10.1126/science.1096706
Publication status	Published - 28 May 2004

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George, S., Rochford, J. J., Wolfrum, C., Gray, S. L., Schinner, S., Wilson, J. C., Soos, M. A., Murgatroyd, P. R., Williams, R. M., Acerini, C. L., Dunger, D. B., Barford, D., Umpleby, A. M., Wareham, N. J., Davies, H. A., Schafer, A. J., Stoffel, M., O'Rahilly, S., & Barroso, I. (2004). A family with severe insulin resistance and diabetes due to a mutation in AKT2. Science, 304(5675), 1325 - 1328. https://doi.org/10.1126/science.1096706

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title = "A family with severe insulin resistance and diabetes due to a mutation in AKT2",

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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George, S, Rochford, JJ, Wolfrum, C, Gray, SL, Schinner, S, Wilson, JC, Soos, MA, Murgatroyd, PR, Williams, RM, Acerini, CL, Dunger, DB, Barford, D, Umpleby, AM, Wareham, NJ, Davies, HA, Schafer, AJ, Stoffel, M, O'Rahilly, S & Barroso, I 2004, 'A family with severe insulin resistance and diabetes due to a mutation in AKT2', Science, vol. 304, no. 5675, pp. 1325 - 1328. https://doi.org/10.1126/science.1096706

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T1 - A family with severe insulin resistance and diabetes due to a mutation in AKT2

AU - George, S

AU - Rochford, J J

AU - Wolfrum, C

AU - Gray, S L

AU - Schinner, S

AU - Wilson, J C

AU - Soos, M A

AU - Murgatroyd, P R

AU - Williams, R M

AU - Acerini, C L

AU - Dunger, D B

AU - Barford, D

AU - Umpleby, A M

AU - Wareham, N J

AU - Davies, H A

AU - Schafer, A J

AU - Stoffel, M

AU - O'Rahilly, S

AU - Barroso, I

PY - 2004/5/28

Y1 - 2004/5/28

N2 - 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.

AB - 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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DO - 10.1126/science.1096706

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VL - 304

SP - 1325

EP - 1328

JO - Science

JF - Science

IS - 5675

ER -

A family with severe insulin resistance and diabetes due to a mutation in AKT2

Abstract

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