Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta).
Glucose homeostasis depends on insulin responsiveness in target tissues, most importantly, muscle and liver. The critical initial steps in insulin action include phosphorylation of scaffolding proteins and activation of phosphatidylinositol 3-kinase. These early events lead to activation of the serine-threonine protein kinase Akt, also known as protein kinase B. We show that mice deficient in Akt2 are impaired in the ability of insulin to lower blood glucose because of defects in the action of the hormone on liver and skeletal muscle. These data establish Akt2 as an essential gene in the maintenance of normal glucose homeostasis.
Cho
H
H
Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mu
J
J
Kim
J K
JK
Thorvaldsen
J L
JL
Chu
Q
Q
Crenshaw
E B
EB
Kaestner
K H
KH
Bartolomei
M S
MS
Shulman
G I
GI
Birnbaum
M J
MJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D018390:Gene Targeting; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006706:Homeostasis; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction
D001786:Blood Glucose; D007328:Insulin; D011518:Proto-Oncogene Proteins; D003847:Deoxyglucose; C494922:Akt2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose