LOSS OF REGULATION BY SYMPATHETIC HEPATIC NERVES OF LIVER-METABOLISM AND HEMODYNAMICS IN CHRONICALLY STREPTOZOTOCIN-DIABETIC RATS

The consequences of autonomic diabetic neuropathy, a common complicati on of chronic diabetes mellitus, have been studied mainly with regard to heart and stomach function. Since the autonomic nervous system also regulates liver carbohydrate metabolism and haemodynamics via hepatic nerves, it was the purpose of this study to examine the function of h epatic nerves in chronically diabetic rats. Diabetes was induced by i. p. injection of streptozotocin. Rat livers were perfused via both port al vein and hepatic artery. Hepatic nerves were stimulated for 2 min u sing a platinum electrode placed around the portal vein and the hepati c artery; in an additional stimulation phase noradrenaline was infused into the portal vein. Stimulation of hepatic nerves as well as portal noradrenaline infusion increased hepatic glucose output and reduced f low in control and in acutely (48-h) diabetic animals, which still had almost normal glycogen content. In addition stimulation also caused a n overflow of noradrenaline into the caval vein. However, nerve stimul ation neither increased glucose output nor decreased flow in 4-month d iabetic rats. In these rats noradrenaline overflow was nearly complete ly abolished and hepatic glycogen content was markedly depleted. Porta l noradrenaline infusion in chronically diabetic rats reduced flow to a similar extent as in controls, yet the increase in glucose output wa s diminished. The lack of nerve stimulation-dependent glucose output, flow reduction and noradrenaline overflow is indicative of a profound loss of function of hepatic autonomic nerves in chronically diabetic r ats.