Hepatic parasympathetic (HISS) control of insulin sensitivity determined by feeding and fasting

In response to insulin, a hormone [hepatic insulin sensitizing substance (H ISS)] is released from the liver to stimulate glucose uptake in skeletal mu scle but not liver or gut. The aim was to characterize dynamic control of H ISS action in response to insulin and regulation of release by hepatic para sympathetic nerves. Insulin action was assessed by the rapid insulin sensit ivity test, where the index is the glucose required (mg/kg) to maintain eug lycemia after a bolus of insulin. Blocking HISS release by interruption of the hepatic parasympathetic nerves by surgical denervation, atropine, or bl ockade of hepatic nitric oxide synthase produced similar degrees of insulin resistance and revealed a similar dynamic pattern of hormone action that b egan 3-4 min after, and continued for 9-10 min beyond, insulin action (50 m U/kg). HISS action accounted for 56.5 +/- 3.5% of insulin action at insulin doses from 5 to 100 mU/kg (fed). We also tested the hypothesis that HISS r elease is controlled by the feed/fast status. Feeding resulted in maximal H ISS action, which decreased progressively with the duration of fasting.