Abnormal insulin production and insulin action are associated with disturbed lipoprotein metabolism, and this linkage might provide an explanation for the relationships between metabolic diseases, such as diabetes and obesity, and cardiovascular disease. As the liver is the exclusive source of endogenous lipoproteins secreted as very-low-density lipoprotein (VLDL), the role of insulin on hepatic VLDL assembly is important. The processes involved in insulin action and lipoprotein assembly are very complex and incompletely understood. Unambiguous definition of their interactions is even more difficult and, as a result, many investigators have taken a reductionist approach by studying these interactions in vitro. However, this approach is not an end in itself. It is not sufficient to know how, for instance, insulin modulates apolipoprotein B (apoB) and lipid interactions within a single hepatocyte in a culture dish or an isolated perfused liver. The full picture will emerge only when we know whether such modulations, if they occur, are affected and modified by other insulin-dependent metabolic processes occurring simultaneously in the whole body. One of the most important of these simultaneous events is the suppression of fatty acid (FA) release from adipose tissue, thus limiting the supply of an important VLDL precursor.

The difference between what insulin is capable of doing in a strictly defined chemical environment in vitro and what insulin actually does in the real world of whole body physiology in vivo strikes at the very core of the controversy surrounding its precise role in hepatic VLDL assembly. In many cases, the consequences of nutritional manipulations and pathophysiological changes which result, amongst other things, in changes in plasma insulin have been attributed to insulin itself rather than to other major associated metabolic perturbations. This paper will deal, first of all, with a review of experiments carried out over a number of years which have sought to define the direct effects of insulin in carefully controlled chemical environments in various types