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

Area of Science:

• Metabolic diseases
• Endocrinology
• Molecular biology

Background:

• Adipocyte fatty acid-binding protein (aP2) deficiency offers protection against diet-induced hyperinsulinemia and insulin resistance.
• The underlying mechanisms for this protective phenotype remain to be fully elucidated.

Purpose of the Study:

• To investigate the role of aP2 in lipolysis and insulin secretion.
• To explore the potential mechanisms linking aP2 to insulin resistance and hyperinsulinemia.

Main Methods:

• Examined lipolysis and insulin secretion in aP2 knockout (aP2-/-) mice and wild-type (aP2+/+) littermates.
• Stimulated lipolysis using beta-adrenergic agonists and measured glycerol and free fatty acid (FFA) release.
• Assessed insulin secretion in response to beta-adrenergic stimulation and other secretagogues (arginine, glyburide).
• Analyzed plasma FFA profiles and aP2 expression in pancreatic islets.

Main Results:

• aP2-/- mice exhibited diminished lipolysis, evidenced by blunted glycerol release and reduced FFA release from adipocytes.
• Beta-adrenergic stimulation resulted in profoundly suppressed insulin secretion in aP2-/- mice.
• Specific alterations in plasma fatty acid profiles (reduced stearic and cis-11-eicoseneic acids, increased palmitoleic acid) were observed in aP2-/- mice.
• Pancreatic beta-cell function was not generally impaired, as responses to arginine and glyburide were similar to controls.
• No aP2 expression was detected in isolated pancreatic islet cells.

Conclusions:

• aP2 plays a critical role in regulating both lipolysis and insulin secretion.
• These findings support the existence of an adipo-pancreatic axis that requires aP2 for proper function.
• aP2's involvement in the pathogenesis of type 2 diabetes may be mediated through its influence on hyperinsulinemia and insulin resistance via lipolysis and insulin secretion regulation.