Abstract
Increased regional sympathetic nerve activity (SNA) triggered by central nervous system (CNS) action of insulin has diverse physiological and pathophysiological implications. However, the molecular events underlying CNS action of insulin in mediating SNA elevation are poorly understood. Previously, we reported that pharmacological inhibition of phosphoinositide 3‐kinase (PI3K) selectively blocked the lumbar SNA response to intracerebroventricular (ICV) administration of insulin. Here, we tested the effect of genetic disruption of p110α catalytic subunit of PI3K on the sympathetic effect of CNS insulin. For this, we utilized a mouse model (p110αD933/WT) carrying a heterozygous mutation in p110α catalytic subunit of PI3K. We used multifiber sympathetic nerve recording to assess the SNA effects of insulin. In wild type mice, ICV administration of insulin (100 μU) caused a robust increase in lumbar SNA (259±37%, n=8). In contrast, ICV insulin failed to increase lumbar SNA in p110αD933/WTmice (−12±21%, n=5, P<0.05 vs. wild type mice). Our data demonstrate that p110α subunit of PI3K is an essential mediator of CNS insulin action to regulate lumbar sympathetic nerve traffic.
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