In late pregnancy insulin-dependent glucose transport phosphorylation is selectively impaired and activation of glycogen synthase by insulin facilitated in skeletal muscles of 24-h starved rats

Aims/hypothesis. We investigated the relation be tween glucose transport/phosphorylation and glycogen synthase activation in individual rat skeletal muscles in response to moderate hyperinsulinaemia in the absence or presence of hyperglycaemia during pregnancy. Methods. Rats were studied on day 20 of pregnancy after 24-h starvation, with unmated rats as controls. Insulin and glucose were infused into conscious rats through an indwelling cannula as specified. Glucose transport/phosphorylation was assessed in vivo using 2-deoxy-[1-H-3]glucose. Glycogen synthase activity was measured in muscle extracts +/- 10 mmol/l glucose-6-phosphate. Results. In unmated rats, stimulation of glucose transport/phosphorylation occurred in response to euglycaemic-hyperinsulinaemia in all muscles studied but activation of glycogen synthase was not observed. Muscle glucose transport/phosphorylation rates during euglycaemic-hyperinsulinaemia after 24-h starvation were lower in pregnant compared with unmated rats, whereas glycogen synthase activation by insulin occurred in two of three fast-twitch muscles of pregnant rats. When insulin and glucose concentrations were matched between the 24-h starved unmated and pregnant groups through variable glucose infusion (15 min), glycogen synthase activities in fast-twitch muscles did not differ between unmated and pregnant groups. The response of glycogen synthase to hyperglycaemia in slow-twitch muscle was, however, greater in the pregnant group. Conclusion/interpretation. Glycogen synthase activation in slow-twitch muscle in response to hyperinsulinaemia after 24-h starvation is enhanced in late pregnancy but the response is critically dependent on glycaemia. Pregnancy is, nevertheless, associated with reduced muscle glucose transport/phosphorylation. This disassociation ensures that available glucose is directed towards the fetus rather than the mother under conditions of moderate hyperinsulinaemia, for example during refeeding after starvation.