Increased insulin sensitivity and hypoinsulinemia in APS knockout mice

Area of Science:

• Molecular Endocrinology
• Metabolic Signaling

Background:

• The adaptor protein APS (Abl-interactor protein with SH2 domain) is tyrosine phosphorylated by the insulin receptor upon insulin stimulation.
• The precise function of APS in insulin signaling pathways remains largely uncharacterized.

Purpose of the Study:

• To investigate the in vivo function of APS in insulin signaling and glucose homeostasis.
• To determine the physiological consequences of APS deficiency on insulin sensitivity.

Main Methods:

• Utilized APS-deficient (APS(-/-)) mice for in vivo studies.
• Performed intraperitoneal insulin tolerance tests and glucose tolerance tests.
• Conducted hyperinsulinemic-euglycemic clamp studies to assess whole-body glucose infusion rates.
• Analyzed insulin signaling components and glucose uptake in 3T3L1 adipocytes and isolated adipocytes.

Main Results:

• APS(-/-) mice exhibited increased insulin sensitivity, evidenced by enhanced blood glucose lowering and increased glucose infusion rates.
• Fasting plasma insulin levels and insulin levels during glucose tolerance tests were reduced in APS(-/-) mice.
• While in vitro studies in 3T3L1 adipocytes showed no direct effect of APS on insulin signaling components or glucose uptake, isolated adipocytes from APS(-/-) mice displayed increased insulin-stimulated glucose transport.
• APS(-/-) mice had elevated serum leptin and adiponectin levels, potentially contributing to enhanced insulin sensitivity.

Conclusions:

• APS deficiency leads to increased systemic insulin sensitivity and improved glucose homeostasis in mice.
• The findings suggest APS plays a critical role in regulating insulin action, possibly through mechanisms independent of direct effects on major insulin signaling molecules in adipocytes.
• Elevated adipokines in APS(-/-) mice may contribute to the observed metabolic phenotype.