The set point for maternal glucose homeostasis is lowered during late pregnancy in the rat: the role of the islet beta-cell and liver

Abstract

SummaryThe aim of this study was to determine the effects of late pregnancy on the ability of insulin to suppress maternal hepatic glucose production in the rat. Unlike in most previous studies, suppression of hepatic glucose production was measured at levels of glycaemia above the relatively hypoglycaemic basal pregnant level. Glucose kinetics were measured using steady-state tracer methodology in chronically catheterised, conscious virgin control and pregnant rats, firstly, during basal and low-dose hyperinsulinaemic euglycaemic clamp conditions and secondly, during a three-step glucose infusion protocol (glucose infusion rates of 0, 60 and 150 ~tmol -kg -1 9 min-1). During the clamps, plasma glucose levels were not different (6.1 +0.4 vs 6.5+0.3 mmol/1, pregnant vs virgin; N.S.), but plasma insulin levels were higher in the pregnant rats (242 + 30 vs 154 + 18 pmol/1, pregnant vs virgin; p < 0.05) most probably due to stimulated endogenous insulin release in this group. Hepatic glucose production was suppressed from basal levels by 41% in virgin and 90 % in pregnant rats. During the glucose infusion studies, at matched insulin levels (147 + 10 vs 152 + 14 pmol/1), but at plasma glucose levels which were much lower in the pregnant rats (5.5 + 0.2 vs 8.4 + 0.6 mmol/l, pregnant vs virgin; p < 0.0001), hepatic glucose production was shown to be suppressed by a similar degree in both groups (41 + 5 vs 51 + 5 % from basal, pregnant vs virgin; N.S.). Both the plasma insulin and percentage suppression of hepatic glucose production dose responses to plasma glucose were markedly shifted to the left indicating that the plasma glucose set point is lowered in pregnancy. In conclusion, suppression of hepatic glucose production by insulin is not impaired and the set point for plasma glucose homeostasis is lowered during late pregnancy in the rat. [Diabetologia (1996) 39: 785-792]

Glucose turnover and gluconeogenesis in human pregnancy.

“…Inasmuch as the maternal weight increased by 16-18% during pregnancy, the total rate of glucose turnover has also increased by this magnitude during late gestation. The mechanism of the decrease in plasma glucose concentration during fasting in pregnancy remains unclear; it has been attributed to the increase in volume of distribution of glucose (18) or a feto-placental glucose steal phenomenon (19,20). The data in this study confirm the previous data and suggest that with advancing gestation, commensurate with the increasing demands by the growing conceptus, there is an increase in total rate of glucose turnover (7).…”

Potential Role of Peroxisome Proliferator-Activated Receptor-α in the Modulation of Glucose-Stimulated Insulin Secretion

“…Hence, although pregnancy is not characterized by hyperglycemia, the placental lactogens and/or prolactin appear to allow a phenotypic shift similar to that induced by elevated glucose to enhance the triggering and amplifying pathways of glucose-induced insulin release, but at a lower extracellular glucose level. Pregnancy-induced increases in ␤-cell glucose sensing and responsiveness are observed ex vivo (48,49,52) as well as in vivo (48,(53)(54)(55), demonstrating that the pregnancyinduced insulin secretory adaptations are predominantly due to a persistent change in islet phenotype.…”

Effects of dietary fat subtypes on glucose homeostasis during pregnancy in rats

“…The increased glucose uptake by the fetal-placental unit will, to the extent that it is insulin-insensitive, lead to overestimation of S during pregnancy. Using the glucose turnover estimates obtained in pregnant rats by Nolan and Proietto [22], and assuming that all of the additional glucose uptake in pregnancy is insulin-insensitive, we calculate that S will be overestimated in pregnancy by 20 %. It should be noted that glucose uptake by the fetal-placental unit might be affected by litter size and total fetal weight.…”