Regulation of β-cell mass and function by the Akt/protein kinase B signalling pathway

被引:75
作者
Elghazi, L. [1 ]
Rachdi, L. [1 ]
Weiss, A. J. [1 ]
Cras-Meneur, C. [1 ]
Bernal-Mizrachi, E. [1 ]
机构
[1] Washington Univ, Sch Med, Dept Internal Med, Div Endocrinol, St Louis, MO 63130 USA
关键词
apoptosis; Akt; beta-cell mass; beta-cell proliferation; diabetes; GSK3; IRS1; IRS2; mTOR; pancreatic islets; PI3K; PKB;
D O I
10.1111/j.1463-1326.2007.00783.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The insulin receptor substrate-2/phosphoinositide 3-kinase (PI3K) pathway plays a critical role in the regulation of beta-cell mass and function, demonstrated both in vitro and in vivo. The serine threonine kinase Akt is one of the promising downstream molecules of this pathway that has been identified as a potential target to regulate function and induce proliferation and survival of beta cells. Here we summarize some of the molecular mechanisms, downstream signalling pathways and critical components involved in the regulation of b-cell mass and function by Akt.
引用
收藏
页码:147 / 157
页数:11
相关论文
共 84 条
[1]   FoxOs at the crossroads of cellular metabolism, differentiation, and transformation [J].
Accili, D ;
Arden, KC .
CELL, 2004, 117 (04) :421-426
[2]   Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action [J].
Aguirre, V ;
Werner, ED ;
Giraud, J ;
Lee, YH ;
Shoelson, SE ;
White, MF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (02) :1531-1537
[3]   The c-Jun amino-terminal kinase pathway is preferentially activated by interleukin-1 and controls apoptosis in differentiating pancreatic β-cells [J].
Ammendrup, A ;
Maillard, A ;
Nielsen, K ;
Andersen, NA ;
Serup, P ;
Madsen, OD ;
Mandrup-Poulsen, T ;
Bonny, C .
DIABETES, 2000, 49 (09) :1468-1476
[4]   Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase [J].
Avruch, J. ;
Hara, K. ;
Lin, Y. ;
Liu, M. ;
Long, X. ;
Ortiz-Vega, S. ;
Yonezawa, K. .
ONCOGENE, 2006, 25 (48) :6361-6372
[5]   FoxO proteins in insulin action and metabolism [J].
Barthel, A ;
Schmoll, D ;
Unterman, TG .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2005, 16 (04) :183-189
[6]  
Bernal-Mizrachi E, 2001, J CLIN INVEST, V108, P1631, DOI 10.1172/JCI200113785
[7]   Defective insulin secretion and increased susceptibility to experimental diabetes are induced by reduced Akt activity in pancreatic islet β cells [J].
Bernal-Mizrachi, E ;
Fatrai, S ;
Johnson, JD ;
Ohsugi, M ;
Otani, K ;
Han, ZQ ;
Polonsky, KS ;
Permutt, MA .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 114 (07) :928-936
[8]   Life and death of the pancreatic β cells [J].
Bonner-Weir, S .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2000, 11 (09) :375-378
[9]   Phosphorylation marks IPF1/PDX1 protein for degradation by glycogen synthase kinase 3-dependent mechanisms [J].
Boucher, MJ ;
Selander, L ;
Carlsson, L ;
Edlund, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (10) :6395-6403
[10]   PKB binding proteins: Getting in on the akt [J].
Brazil, DP ;
Park, J ;
Hemmings, BA .
CELL, 2002, 111 (03) :293-303