Regulation of pancreatic beta-cell growth and survival by the serine/threonine protein kinase Akt1/PKBalpha.
The physiological performance of an organ depends on an interplay between changes in cellular function and organ size, determined by cell growth, proliferation and death. Nowhere is this more evident than in the endocrine pancreas, where disturbances in function or mass result in severe disease. Recently, the insulin signal-transduction pathway has been implicated in both the regulation of hormone secretion from beta cells in mammals as well as the determination of cell and organ size in Drosophila melanogaster. A prominent mediator of the actions of insulin and insulin-like growth factor 1 (IGF-1) is the 3'-phosphoinositide-dependent protein kinase Akt, also known as protein kinase B (PKB). Here we report that overexpression of active Akt1 in the mouse beta cell substantially affects compartment size and function. There was a significant increase in both beta-cell size and total islet mass, accompanied by improved glucose tolerance and complete resistance to experimental diabetes.
Tuttle
R L
RL
Howard Hughes Medical Institute, Department of Internal Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Gill
N S
NS
Pugh
W
W
Lee
J P
JP
Koeberlein
B
B
Furth
E E
EE
Polonsky
K S
KS
Naji
A
A
Birnbaum
M J
MJ
D000818:Animals; D002455:Cell Division; D048429:Cell Size; D002470:Cell Survival; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000517:prevention & control; D004789:Enzyme Activation; D005260:Female; D007515:Islets of Langerhans / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats
D011518:Proto-Oncogene Proteins; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt