In vivo insulin resistance during pregnancy in the rat

Leturque, Armelle; Ferré, Pascal; Satabin, P.; Kervran, A.; Girard, Jean

doi:10.1007/bf00253179

Cited by 76 publications

(58 citation statements)

References 25 publications

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“…In this regard, Hay et al (13) have shown a constant weight-specific glucose utilization rate throughout pregnancy in chronically catheterized, conscious rabbits. Similar results have been obtained for the pregnant rat (23) in which additional evidence supports a decreased insulin sensitivity in late gestation for the liver (22).…”

Section: Discussionsupporting

confidence: 86%

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Some Aspects of Maternal Metabolism Throughout Pregnancy in the Conscious Rabbit

1984

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SummaryStudies of maternal metabolism during pregnancy have focused principally upon the latter half of gestation. However, maternal metabolic adaptations to pregnancy may occur at all stages of pregnancy. To study maternal metabolism throughout pregnancy, we developed a chronically catheterized rabbit model in which animals could be studied under conscious, stress-free conditions when nonpregnant and then serially throughout pregnancy.Anesthesia produced marked hyperglycemia. In contrast, chronic catheterization and daily handling did not affect blood concentrations of glucose, lactate, ketone bodies, or free fatty acids, or food intake. Glucose concentration decreased with pregnancy to a value at term equal to 85% of the prepregnancy value. Lactate concentration rose significantly in the second half of pregnancy but changes in free fatty acids and ketoacid levels were not significant. These results are discussed from a comparative physiologic point of view, emphasizing the unique aspects of rabbit metabolism during pregnancy and the importance of performing such studies under conscious, stress-free conditions.The impact of pregnancy upon maternal metabolism of carbohydrates and lipids has been studied in the rat (14,20), guinea pigs (I I, 37), and man (8,18,30). In these species, most studies were performed over the latter third of gestation. It is probable that the timing and the magnitude ofmaternal metabolic changes during pregnancy may be related to such factors as the growth rate of the fetus and the placenta, the fetal and placental mass and metabolic rate at different stages of pregnancy, and the maternal diet. In particular, animal species with a relatively short gestation that produce a large fetal to maternal mass ratio at term (i.e., guinea pig, 0.50; rat, 0.17; and rabbit, 0.15) are of interest with regard to the maternal metabolic changes which occur during the entirety of gestation.The majority of metabolic studies during pregnancy have involved surgical, anesthetic, and handling stress. In particular, in the rabbit there have been no studies describing maternal metabolism at any time of pregnancy under chronic, stress-free, steady state conditions. The present paper describes our results in developing techniques for chronic catheterization of rabbits prior to pregnancy, permitting metabolic studies in the conscious

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Section: Discussionsupporting

confidence: 86%

“…At term in pregnant rats, plasma hsulin levels are higher (14,20,32) or unchanged (22) compared to those of nonpregnant animals. In pregnant women, preparturn values are slightly higher than postpartum values (28).…”

Section: Discussionmentioning

confidence: 88%

Some Aspects of Maternal Metabolism Throughout Pregnancy in the Conscious Rabbit

1984

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“…It was found here, in agreement with previous reports (19), that sustained euglycemia-hyperinsulinemia decreases overall insulin sensitivity in virgin rats and reverts the insulin resistance condition (19) normally present in pregnant animals (5,6,31,32). Furthermore, the present study shows, for the first time, that in pregnant rats, mammary gland displays high insulin-dependent glucose uptake under hyperinsulinemia, caused by either the euglycemic-hyperinsulinemic clamp or by the continuous glucose infusion.…”

Section: Discussionsupporting

confidence: 93%

Changes in the Kinase Activity of the Insulin Receptor Account for an Increased Insulin Sensitivity of Mammary Gland in Late Pregnancy¹

et al. 1998

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Mammary gland is an organ that undergoes cycles of growth, differentiation, and function during pregnancy and lactation. Although it is known that the gland enhances its sensitivity to insulin during lactation, it remains to be investigated whether this increased sensitivity develops during pregnancy and which are the molecular mechanisms underlying such a change. To address this issue, virgin and late-pregnant rats were subjected to a continuous infusion with 50% glucose for 72 h to produce a prolonged hyperinsulinemic-euglycemic condition. Insulin sensitivity in mammary gland was determined as the glucose utilization index by using 2-[ 3 H]-deoxyglucose. Furthermore, binding characteristics and kinase activity were studied by means of both [125 I]insulin binding and in vitro phosphorylation studies with insulin receptors partially purified from mammary gland.Whereas the glucose utilization index in mammary gland from nonpregnant rats remained unaffected by hyperinsulinemia, glands from pregnant rats displayed a high insulin-dependent glucose uptake. This effect was not paralleled by changes in the binding characteristics of insulin to the high-affinity receptor, suggesting that the high insulin sensitivity of mammary gland in pregnancy is not accounted for by changes at the level of hormone-receptor interaction. Autophosphorylation studies showed that insulin-stimulated kinase activity of insulin receptors from mammary gland was 6-and 20-fold higher in pregnant than in virgin animals under normo-and hyperinsulinemic conditions, respectively. Moreover, insulin dose-response curves revealed that the efficacy of insulin to stimulate kinase activity of the insulin receptor was markedly higher in pregnant than in virgin rats, whereas its potency (ED 50 ϳ 15 nM) was not changed. These data, therefore, show that mammary glands develop increased insulin sensitivity during late pregnancy, caused by an augmented kinase activity of the insulin receptor. (Endocrinology 139: 520 -526, 1998)

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“…In ex cess, it decreases carbohydrate utilization and impairs glucose uptake into cells [4], These effects result in glucose intolerance which, in turn, stimulates insulin secretion. During pregnancy, maternal tissues become less sen sitive to insulin so that glucose is diverted to the fetoplacental unit [5], During lactation, increased insulin resistance of maternal tis sues, other than the milk glands, achieves a similar goal: increased utilization of glucose by the milk gland [6] to meet the nutritional requirements of the offspring.…”

Section: Introductionmentioning

confidence: 99%

Effects of Porcine Growth Hormone on Pregnancy and Fetal/Neonatal Development in the Rat

Spence

Mattson²,

Vetter³

et al. 1995

Neonatology

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Porcine growth hormone was given subcutaneously twice daily to two groups of 20 females at dose levels of 0.5 and 2.5 IU/kg (1 and 5 IU/kg/day). A control group of 20 females was similarly treated with vehicle. The females were given either vehicle or porcine growth hormone from gestation day (GD) 6 through GD 21, for 10 females that were cesarean sectioned, or through lactation day (LD) 21, for 10 females scheduled for natural delivery. There were no deaths, abortions, or drug-related physical signs in any treatment group. Drug-related effects during gestation were limited to significant (p < 0.05) pharmacologically mediated increases in Fo maternal body weight gain during GD 6-20 in the 2.5-IU/kg group, approximately 24% above controls. During LD 0-21, there were significant (p < 0.05) dose-related increases in average maternal body weight gain in the 0.5- and 2.5-IU/kg groups (72 and 200% above controls, respectively). Consistent with these findings, there were dose-dependent increases in maternal serum growth hormone and IGF-1 levels noted on GD 21 and LD 21 in both drug-treated groups. There were no drug-related effects on embryonal/fetal survival, GD 21 fetal body weight, placental weight, fetal femur length and width, or fetal morphology as determined by external, visceral, and skeletal examinations. There were no drug-related effects on Fi pup mortality, physical signs, body weight, biparietal diameter, liver weight, and femur length or width. These data suggest that subcutaneous administration of growth hormone to pregnant and lactating rats, at a dose that produces significant (p < 0.05) increases in maternal body weight gain and serum IGF-1 levels, has no apparent effect on embryonal/fetal development or preweaning growth.

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In vivo insulin resistance during pregnancy in the rat

Cited by 76 publications

References 25 publications

Some Aspects of Maternal Metabolism Throughout Pregnancy in the Conscious Rabbit

Some Aspects of Maternal Metabolism Throughout Pregnancy in the Conscious Rabbit

Changes in the Kinase Activity of the Insulin Receptor Account for an Increased Insulin Sensitivity of Mammary Gland in Late Pregnancy¹

Effects of Porcine Growth Hormone on Pregnancy and Fetal/Neonatal Development in the Rat

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In vivo insulin resistance during pregnancy in the rat

Cited by 76 publications

References 25 publications

Some Aspects of Maternal Metabolism Throughout Pregnancy in the Conscious Rabbit

Some Aspects of Maternal Metabolism Throughout Pregnancy in the Conscious Rabbit

Changes in the Kinase Activity of the Insulin Receptor Account for an Increased Insulin Sensitivity of Mammary Gland in Late Pregnancy1

Effects of Porcine Growth Hormone on Pregnancy and Fetal/Neonatal Development in the Rat

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Changes in the Kinase Activity of the Insulin Receptor Account for an Increased Insulin Sensitivity of Mammary Gland in Late Pregnancy¹