Insulin stimulation of hepatic triacylglycerol secretion and the etiology of insulin resistance

The recent observations that insulin can either stimulate or inhibit triacy lglycerol secretion by the liver, depending on prior metabolic (possibly in sulinemic) state, have rationalized the many apparently contradictory obser vations, obtained over the past three decades, on the effects of the hormon e on this aspect of hepatic metabolism. Extrapolation to the situation in v ivo suggests that frequent stimulation of insulin secretion may result in a chronic stimulation of VLDL secretion, and increased delivery of acyl moie ties to muscle, where they induce insulin resistance if provided in excess of the oxidative needs (mostly due to exercise) of the tissue. High fructos e/sucrose diets, which also stimulate hepatic VLDL secretion, will have the same effect, especially if consumed frequently during the diurnal cycle. D ue to the quantitative importance of muscle as a site for insulin-sensitive glucose metabolism, these effects may initiate the metabolic vicious cycle that results in the development of the metabolic syndrome, well in advance of overt obesity or the diagnosis of type-2 diabetes.