Control of glucose metabolism in isolated acini of the lactating mammary gland of the rat. The ability of glycerol to mimic some of the effects of insulin

Abstract

Inhibition of glucose uptake by acetoacetate and relief of this inhibition by insulin found previously in slices of rat mammary gland [Williamson, McKeown & Ilic (1975) Biochem. J. 150. 145-152] was confirmed in acini, which represent a more homogeneous population of cells. Glycerol (1mM) behaved like insulin (50 minuits/ml) in its ability to relieve the inhibition of glucose (5 mM) utilization caused by acetoacetate (2 mM) in acini. Both glycerol and insulin reversed the increase in [citrate] and the decrease in [glycerol 3-phosphate] and the [lactate]/[pyruvate] ratio in the presence of acetoacetate. Lipogenesis from 3H2O, [3-14C] acetoacetate, [1-14C]- and [6-14C]-glucose was stimulated, whereas 14CO2 formation from [3-14C]acetoacetate was decreased. Neither insulin nor glycerol relieved the acetoacetate inhibition of glucose uptake when lipogenesis was inhibited by 5-(tetradecyloxy)-2-furoic acid. From measurements of [3-14C]acetoacetate incorporation into lipid in the various situations it is suggested that a cytosolic pathway for acetoacetate utilization may exist in rat mammary gland. In the absence of acetoacetate, glycerol inhibited glucose utilization by 60% and increased both [glycerol 3-phosphate] and the [lactate/[pyruvate] ratio. Possible ways in which glycerol may mimic the effects of insulin are discussed.

Regulation of lactating-rat mammary-gland lipogenesis by insulin and glucagon in vivo. The role and site of action of insulin in the transition to the starved state

“…Its mode of regulation, as in other tissues, may be linked to ketone-body metabolism through changes in citrate concentrations (Randle et al, 1964). Inhibition of glucose utilization by ketone bodies in isolated acini can be reversed by insulin, with concomitant lowering of citrate concentrations (Robinson & Williamson, 1977). The findings in the present study suggest that this mechanism may occur in vivo, since starvation causes an increase in circulating ketonebody concentrations (Table 1) and a rise in citrate concentrations in the mammary gland (Table 2).…”

Time course of changes in plasma glucose and insulin concentrations and mammary-gland lipogenesis during re-feeding of starved conscious lactating rats

“…Short-term starvation inactivates lipogenesis in the gland , and re-feeding with chow diet leads to a rapid restoration of lipogenic activity (Munday & Williamson, 1981;Bussmann et al, 1984;Williamson et al, 1985). Insulin is a key factor in the regulation of lipogenesis in vivo in the mammary gland (Robinson & Williamson, 1977;Robinson et al, 1978;Burnol et al, 1983;, and the restoration of lipogenesis during re-feeding is prevented by insulin deficiency (Robinson et al, 1978). However, the temporal changes in circulating insulin concentrations during re-feeding have not been documented in the lactating rat, and thus it is not known if the restoration of lipogenesis in the mammary gland occurs in synchrony with increased plasma insulin concentrations, or whether it involves changes in the rate of insulin delivery to the gland (via increased blood flow) or in the insulin-sensitivity of the tissue itself.…”

Synthesis of fat in response to alterations in diet: Insights from new stable isotope methodologies

“…This formulation may not always be correct for humans, however. In addition, other specialized tissues may also perform DNL under certain circumstances, e.g., lactating mammary gland (14).…”

“…(7) DNL becomes important in specialized tissues or under special conditions. The lactating mammary gland appears to have a very active DNL pathway, at least in animal models (14). The metabolic source of lipids in breast milk of humans has not yet been established, however.…”