Acute meal‐induced changes in hepatic glycerolipid metabolism are unimpaired in severely diabetic rats: implications for the role of insulin

Abstract

The effect of food intake on the partitioning of diacylglyceroi between phospholipid and triacylglycerol synthesis, and on the fractional rate of secretion of triacylglycerol was studied in starved-refed diabetic rats by using the technique of selective labelling of hepatic fatty acids in vivo. Acute and phasic responses in these parameters similar to those observed previously in normal animals were obtained, in spite of the absence of any insulin response to refeeding. Labelling of the major phospholipids (phosphatidylcholine and phosphatidylethanolamine) increased markedly at the expense of triacylglycerol labelling. In addition, the fractional rate of secretion of newlylabelled triacylglycerol was decreased. The data suggest that insulin is not obligatorily involved in any decrease in hepatic triacylglycerol secretion in the prandial period, but that it may act synergistically with other meal-induced signals to mediate this effect in normal animals.ever, the role of insulin in the control of TAG secretion has proved controversial, partly because some workers have found that the hormone stimulates TAG secretion in the perfused liver [11] and in prolonged cultures of rat hepatocytes [12] and partly because conditions eharacterised by hyperinsulinaemia in vivo are associated with an increased rate of TAG secretion by the liver (see e.g. [13]).Therefore, in the present study we have employed the technique of selective labelling of hepatic fatty acids in vivo to address the question as to whether a normal insulin secretory response is required for meal-induced changes in the partitioning of DAG and TAG to occur. The results suggest that insulin does not play an obligatory role in these responses, as they are unimpaired in severely diabetic rats given a meal after a period of starvation.

Carnitine palmitoyltransferase 1: Central to cell function

“…And secondly that, the only parameter that showed the same profiles as those for ketone body formation was the change in malonyl‐CoA sensitivity of CPT 1. These results were confirmed by studies of the changes in the partitioning of fatty acids between oxidation and esterification when studied in real time through the specific labelling of hepatocyte fatty acids in awake, unrestrained rats exposed to normal physiological perturbations16–19.…”

The malonyl-CoA–long-chain acyl-CoA axis in the maintenance of mammalian cell function

“…Such a mechanism may be required for the maintenance of a substantial rate of TAG secretion under conditions of low hepatic malonylCoA levels, in spite of the diminished overall rate of TAG synthesis. In support of this proposition is the observation that, in i o, in spite of the much lower proportion of hepatic fatty acids utilized for overall TAG synthesis in insulin-deficient states, the fractional secretion rate of fatty acids newly incorporated into TAG remains high [92][93][94][95][96]. Whether raised malonyl-CoA concentrations inhibit TAG secretion by limiting acylcarnitine formation is difficult to ascertain at present, especially as a strong relationship between the rate of de no o fatty acid synthesis and VLDL TAG secretion is invariably observed [97].…”

Role of insulin in hepatic fatty acid partitioning: emerging concepts

“…This conclusion appeared to be supported by the fact that the effects were slightly more pronounced and longer-lasting in meal-fed rats, in which the prandial release of insulin is more pronounced. In an attempt to determine more directly the role of insulin in the diversion of acyl-CoA away from TAG synthesis and secretion during the prandial period in i o, refeeding experiments were performed on starved-refed streptozotocin-diabetic rats [172]. In spite of a much attenuated insulin-secretory response to food intake [86], the liver of these animals showed the same pattern of acute changes in the partitioning of DAG and in the fractional rate of secretion of TAG (see Table 1 and Figure 5).…”

“…Thus, both effects observed in i o on the partitioning of DAG and TAG can be mimicked in itro by exposure of isolated hepatocytes to conditions that result in a 10-20 % increase in cell volume. These observations may explain why the changes in glycerolipid metabolism that accompany food intake are unimpaired in severely diabetic rats [172], especially since the rate of Na + co-transport of amino acids such as glutamine and alanine is induced several-fold in diabetic-rat hepatocytes [177]. They do not exclude the possibility, however, that in the normal animal the effects of increased portal substrate\ion concentrations on cell volume could act synergistically with the effects of insulin.…”