The set point for maternal glucose homeostasis is lowered during late pregnancy in the rat: the role of the islet beta-cell and liver.
The 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 mumol.kg-1. min-1). During the clamps, plasma glucose levels were not different (6.1 +/- 0.4 vs 6.5 +/- 0.3 mmol/l, pregnant vs virgin; N.S.), but plasma insulin levels were higher in the pregnant rats (242 +/- 30 vs 154 +/- 18 pmol/l. 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/l), 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.
Nolan
C J
CJ
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Victoria, Australia.
Proietto
J
J
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000096:biosynthesis*; D015309:Glucose Clamp Technique; D006706:Homeostasis / Q000502:physiology*; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose