The role of mouse Akt2 in insulin-dependent suppression of adipocyte lipolysis in vivo.
OBJECTIVE
The release of fatty acids from adipocytes, i.e. lipolysis, is maintained under tight control, primarily by the opposing actions of catecholamines and insulin. A widely accepted model is that insulin antagonises catecholamine-dependent lipolysis through phosphorylation and activation of cAMP phosphodiesterase 3B (PDE3B) by the serine-threonine protein kinase Akt (protein kinase B). Recently, this hypothesis has been challenged, as in cultured adipocytes insulin appears, under some conditions, to suppress lipolysis independently of Akt.


METHODS
To address the requirement for Akt2, the predominant isoform expressed in classic insulin target tissues, in the suppression of fatty acid release in vivo, we assessed lipolysis in mice lacking Akt2.


RESULTS
In the fed state and following an oral glucose challenge, Akt2 null mice were glucose intolerant and hyperinsulinaemic, but nonetheless exhibited normal serum NEFA and glycerol levels, suggestive of normal suppression of lipolysis. Furthermore, insulin partially inhibited lipolysis in Akt2 null mice during an insulin tolerance test (ITT) and hyperinsulinaemic-euglycaemic clamp, respectively. In support of these in vivo observations, insulin antagonised catecholamine-induced lipolysis in primary brown fat adipocytes from Akt2-deficient mice.


CONCLUSIONS
These data suggest that suppression of lipolysis by insulin in hyperinsulinaemic states can take place in the absence of Akt2.
The Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania, Philadelphia, PA, USA.
Shlomit
S
Koren
Lisa M
LM
DiPilato
Matthew J
MJ
Emmett
Abigail L
AL
Shearin
Qingwei
Q
Chu
Bob
B
Monks
Morris J
MJ
Birnbaum
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D007004:Hypoglycemic Agents; D007328:Insulin; C494922:Akt2 protein, mouse; D051057:Proto-Oncogene Proteins c-akt