Effects of subfornical organ lesions on sympathetic nerve responses to insulin

Although insulin exerts potent excitatory effects on the sympathetic nervous system, the mechanisms of insulin-induced activation remain unclear. To demonstrate a central nervous system site of sympathoexcitation, we recently found that destruction of tissues surrounding the anteroventral third ventricle region abolishes elevations in sympathetic nerve activity to intravenous insulin administration. Anteroventral third ventricle lesions may eliminate sympathoexcitation by destroying cell bodies in the lesioned area or by interrupting fibers of passage from the subfornical organ. To determine whether the lesions abolish sympathetic increases by disrupting efferent fibers from the subfornical organ, we measured lumbar sympathetic activity in anesthetized anteroventral third ventricle-lesioned (n = 4) and subfornical organ-lesioned (n = 12) rats before and during intravenous insulin at 0.13 U/h while maintaining euglycemia. Additional sham-lesioned rats received infusion of insulin (n = 10) and the vehicle for insulin (n = 10). Insulin administration in sham-lesioned rats elevated lumbar activity from 100% to 171 +/- 14% (+/-SE), whereas vehicle infusion did not alter sympathetic activity (100% to 113 +/- 11%). In anteroventral third ventricle-lesioned rats, insulin failed to increase sympathetic nerve activity (100% to 119 +/- 14%). Importantly, rats with subfornical organ lesions had increases in nerve activity that were indistinguishable from increases observed in insulin-infused sham-lesioned rats (100% to 163 +/- 21%). These findings indicate that whereas the anteroventral third ventricle region itself is crucial for sympathoexcitation to insulin, the subfornical organ and fibers originating from the subfornical organ traversing the anteroventral third ventricle area are not essential in mediating elevations in lumbar sympathetic nerve activity to hyperinsulinemia.