The role of mouse Akt2 in insulin-dependent suppression of adipocyte lipolysis in vivo

Diabetologia. 2015 May;58(5):1063-70. doi: 10.1007/s00125-015-3532-9. Epub 2015 Mar 5.


Aim/hypothesis: 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/interpretation: These data suggest that suppression of lipolysis by insulin in hyperinsulinaemic states can take place in the absence of Akt2.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Animals
  • Hypoglycemic Agents / pharmacology*
  • Insulin / pharmacology*
  • Insulin Resistance / physiology
  • Lipolysis / drug effects
  • Lipolysis / physiology*
  • Mice
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*


  • Hypoglycemic Agents
  • Insulin
  • Akt2 protein, mouse
  • Proto-Oncogene Proteins c-akt