Insulin stimulates triacylglycerol secretion by perfused livers from fed rats but inhibits it in livers from fasted or insulin-deficient rats - Implications for the relationship between hyperinsulinaemia and hypertriglyceridaemia

We determined whether the direction of the acute effect of insulin on hepat ic triacylglycerol secretion is dependent on the prior physiological state or on the in vitro experimental system used. The effect of insulin on triac ylglycerol secretion was studied using perfused livers isolated from rats u nder three metabolic conditions: fed normo-insulinaemic, 24-h fasted and fe d, streptozotocin-diabetic (insulin-deficient). Insulin acutely activated t riacylglycerol secretion (by 43%) in organs from fed, normo-insulinaemic an imals, whereas it inhibited triacylglycerol secretion in livers isolated fr om fasted or insulin-deficient rats (by 30 and 33%, respectively). By contr ast, in 24-h-cultured hepatocytes insulin invariably acutely inhibited tria cylglycerol secretion irrespective of the metabolic state of the donor anim als. It is concluded that the use of perfused livers enables the observatio n of a switch in the direction of insulin action on hepatic triacylglycerol secretion from stimulatory, in the normo-insulinaemic state, to inhibitory in the fasting or insulin-deficient state. The possible implications of th is switch for the relationship between hyperinsulinaemia, increased hepatic very-low-density lipoprotein-triacylglycerol secretion and hypertriglyceri daemia observed in vivo are discussed.