Altered insulin secretion associated with reduced lipolytic efficiency in aP2-/- mice

Diabetes. 1999 Oct;48(10):1987-94. doi: 10.2337/diabetes.48.10.1987.


Recent studies have shown that genetic deficiency of the adipocyte fatty acid-binding protein (aP2) results in minor alterations of plasma lipids and adipocyte development but provides significant protection from dietary obesity-induced hyperinsulinemia and insulin resistance. To identify potential mechanisms responsible for this phenotype, we examined lipolysis and insulin secretion in aP2-/- mice. Beta-adrenergic stimulation resulted in a blunted rise of blood glycerol levels in aP2-/- compared with aP2+/+ mice, suggesting diminished lipolysis in aP2-/- adipocytes. Confirming this, primary adipocytes isolated from aP2-/- mice showed attenuated glycerol and free fatty acid (FFA) release in response to dibutyryl cAMP. The decreased lipolytic response seen in the aP2-/- mice was not associated with altered expression levels of hormone-sensitive lipase or perilipin. The acute insulin secretory response to beta-adrenergic stimulation was also profoundly suppressed in aP2-/- mice despite comparable total concentrations and only minor changes in the composition of systemic FFAs. To address whether levels of specific fatty acids are different in aP2-/- mice, the plasma FFA profile after beta-adrenergic stimulation was determined. Significant reduction in both stearic and cis-11-eicoseneic acids and an increase in palmitoleic acid were observed. The response of aP2-/- mice to other insulin secretagogues such as arginine and glyburide was similar to that of aP2+/+ mice, arguing against generally impaired function of pancreatic beta-cells. Finally, no aP2 expression was detected in isolated pancreatic islet cells. These results provide support for the existence of an adipo-pancreatic axis, the proper action of which relies on the presence of aP2. Consequently, aP2's role in the pathogenesis of type 2 diabetes might involve regulation of both hyperinsulinemia and insulin resistance through its impact on both lipolysis and insulin secretion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipocytes / metabolism
  • Adipose Tissue / metabolism
  • Animals
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cells, Cultured
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Fatty Acids / metabolism*
  • Gene Expression Regulation
  • Insulin / metabolism*
  • Insulin Secretion
  • Lipolysis*
  • Mice
  • Mice, Inbred C57BL
  • Myelin P2 Protein / metabolism
  • Myelin P2 Protein / physiology*
  • Neoplasm Proteins*
  • Nerve Tissue Proteins*
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, Adrenergic, beta-3


  • Carrier Proteins
  • Fabp5 protein, mouse
  • Fabp7 protein, mouse
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Fatty Acids
  • Insulin
  • Myelin P2 Protein
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Receptors, Adrenergic, beta
  • Receptors, Adrenergic, beta-3