Glucagon metabolism in nonhuman primate pregnancy

Chez, Ronald A.; Mintz, Daniel H.; Epstein, Michael F.; Fleischman, Alan R.; Oakes, Gary K.; Hutchinson, Donald L.

doi:10.1016/0002-9378(74)90612-7

Cited by 23 publications

(14 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As with insulin, glucagon has been identified in the fetal pancreas from early in gestation and the evidence would suggest that glucagon is not transferred across the placenta (9, 12). Chez et al (9) have shown in the normal monkey pregnancy, fetal hypoglycemia, hyperglycemia, and hyperalanemia are not associated with changes in fetal plasma glucagon concentration. Epstein et al (10) found no increase in fetal glucagon in the rhesus monkey made glucoseintolerant with streptozotocin.…”

Section: Discussionmentioning

confidence: 95%

Fetal and Maternal Hormonal Response to Starvation in the Ewe

et al. 1980

View full text Add to dashboard Cite

SummaryFive ewes 90-130 days of gestation with chronically indwelling fetal catheters were studied. Blood samples were drawn each morning simultaneously from the maternal femoral artery, fetal femoral artery, and fetal umbilical vein. Total starvation was begun after blood samples had been drawn on the 3rd morning, but water was given ad libitum. The mean maternal arterial plasma glucose concentration before starvation (73.4 2 31.0 (SEM) mg/100 ml plasma HzO) fell to 54.8 f 5.2 mg/100 ml (P < 0.01) after 24 hr of fasting and to 37.5 + 1.6 mg/100 ml (P < 0.001) by 72 hr of fasting. The maternal arterial fructose concentration was low in both the fed (2.9 f 0.4 mg/100 ml) and fasted states (1.8 + 0.5 mg/100 ml, day 3). The maternal arterial insulin concentration fell early in fasting from a mean of 27.9 + 3.9 uU/ml on 2 days before starvation to 12.4 + 1.8 uU/ml after 24 hr of fasting (P < 0.005) and remained low for the duration of the 7-day fasting period. The mean maternal arterial glucagon concentration in the fed state was 112 + 20 pg/ml and did not change significantly throughout the 7 days of maternal fasting.Fetal arterial plasma glucose was much lower than maternal levels (mean 18.4 + 1.1 mg/100 ml plasma Hz0 in the fed state), decreased to 12.1 + 1.4 mg/100 ml after 24 hr of fasting ( P < 0.05) and did not change significantly after the 1st day of fasting.The whole blood fructose concentration in the fetal artery was high in the fed state (71.7 + 11.5 mg/100 ml, mean 2 days before fasting) and fell quickly during starvation (54.2 2 3.4 mg/100 ml after 48 hr). The fructose concentration did not change further for the duration of the fasting period. The fetal arterial insulin concentration was lower than the maternal (19.4 + 1.0 uU/ml in the fed state and did not fall dramatically after fasting as the mother did. After 24 hr of fasting, the fetal insulin was 15.0 + 1.5 uU/ml ( P < 0.005) and remained low throughout the fast. The umbilical venous-arterial differences of insulin were statistically different from 0 in both fed (mean -1.4 f 0.3 u U / d , P < 0.005) and fasted state (mean -1.4 + 0.5 uU/d, P < 0.02), with the fetal artery greater than the umbilical vein in 25 of 28 measurements. The fetal arterial concentration of glucagon was lower than in the ewe (32 f 7 pg/ml) and also did not change significantly during starvation.There was a good correlation of the plasma glucose and insulin concentrations for: both the fetus and the ewe. Analvsis of ~ooled fetal and maternal regression lines for insulin-glucos~relatidnships reveals no difference in the slow (maternal 0.48. fetal 0.48). but a statistically significant differeice'in the y intercept (mateinal -7.70, fetal 8.65, P < 0.005), with the fetal curve shifted to the left.The excellent correlation between plasma glucose and insulin concentration throughout the fed and fasted periods suggests that the decrease in fetal plasma glucose and the decreased utilization of exogenous glucose by the fetus is mediated by fetal insulin level. Although the respons...

show abstract

Section: Discussionmentioning

confidence: 95%

Fetal and Maternal Hormonal Response to Starvation in the Ewe

et al. 1980

View full text Add to dashboard Cite

show abstract

“…There is very poor stimulation of glucagon secretion by the fetal pancreas by L-alanine and hypoglycaemia which are potent secretagogues in adult animals (Chez, Mintz, Epstein, Oakes & Hutchison, 1974). Although glucagon is a more effective glycogenolytic agent in adult liver than catecholamines (Sokal, Sarcione & Henderson, 1964), pharmacological doses of glucagon are needed to cause hyperglyeaemia and endogenous glucose output in the fetus (Devaskar, Ganguli, Syer, Devaskar & Sperling, 1984) and this glucagon resistance is known to persist until after birth (Ganguli, Sinha, Sterman, Harris & Sperling, 1983).…”

Section: Introductionmentioning

confidence: 99%

Release of glucose from the liver of fetal and postnatal sheep by portal vein infusion of catecholamines or glucagon.

Apatu

Barnes

1991

The Journal of Physiology

View full text Add to dashboard Cite

SUMMARY1. The blood flow to the liver in fetuses near term, newborn and adult sheep was measured by the Fick principle, using radionuclide-labelled plastic microspheres, before and during infusion of adrenaline, noradrenaline or glucagon.2. Glucose output and lactate consumption by the liver in sheep of each age group were calculated by application of the Fick principle using the concentration gradients of these metabolites measured in blood samples obtained, simultaneously with blood flow measurements, from catheters chronically implanted in the inflow and outflow vessels of the liver.3. Catecholamines were infused into the portal vein of fetuses near term at a rate comparable with that at which they are known to be secreted in the sheep fetus during moderate to severe hypoxia. The cardiovascular and metabolic responses to these infusions were found to be comparable with those that occur in the fetus during hypoxia.4. Catecholamines increased glucose output from the liver in all except the immediate post-partum animals. Catecholamines were less effective than glucagon in promoting glucose release. The mean increments in glucose output during adrenaline infusion were 0055+0-015 mmol min-(100 g liver)-1 in the fetus, 0-122+ 0024 mmol min-(100 g)-1 in the 2-week-old lambs, 0078+0019 mmol min-' (100 g)-' in young lambs and 0-049+0-012 mmol min-' (100 g)-' in the adult sheep.During glucagon infusion the mean glucose output increments were 0-146 + 0023 mmol min-1 (100 g)-in the fetus, 0-274+0-085 mmol min-(100 g)-1 in the 2-week-old and young lambs and 0 180+0-054 mmol min-' (100 g)-1 in the adult. Adrenaline was more potent than noradrenaline, suggesting that the major glycogenolytic response might be f-receptor mediated.5. In the immediate newborn period the output of glucose from the liver was high (0-20 + 0-05 mmol min-' (100 g liver)-' and was not statistically significantly increased by infusion either of glucagon or of catecholamines which resulted in similar increments of glucose output of about 04128 +0-133 mmol min-' (100 g)-1. It is probable that the high output of glucose reflected the high endogenous circulating levels of catecholamines and glucagon in these animals at birth and that further infusions failed to add significantly to the already near-maximal glucose release. R. S. K. APATU AND R. J. BARNES absence of high levels of circulating catecholamines and glucagon in the resting fetus but also may indicate a deficiency in either the receptor mechanism for catecholamines or of the intracellular second messenger system for glycogenolysis. The greater effectiveness of glucagon (than adrenaline) as a mediator of glucose release in these animals tends to support the idea of a fl-receptor rather than a second messenger deficiency. It is postulated that a deficiency of hepatic ,-adrenergic receptors, provided that it can be corrected in time for birth, would help to protect glycogen stores in the liver in utero.

show abstract

“…Glucose is used as a major source of metabolic energy in the human fetus (2)(3)(4) and a glucose imbalance, in addition to affecting the growth of embryonic tissue, may well result in developmental abnormalities such as macrosomia, malformations, and increased rate of stillbirths, as is manifested in pregnancies of diabetic women. Insulin, a regulator of glucose metabolism, is an essential growth factor for fast-growing mammalian tissues, including human embryonic tissues (2-4); however maternal insulin does not cross the blood/placental barrier (5)(6)(7)(8). Although it has not been established that insulin or an insulin-like growth factor is necessary for the early development of the human fetus in utero, such a requirement is not unlikely.…”

mentioning

confidence: 99%

Insulin-related genes expressed in human placenta from normal and diabetic pregnancies.

Liu¹,

Wang²,

Mills³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Rapid growth of human fetal tissues requires insulin or insulin-like growth factors. A high rate of human fetal growth occurs between implantation and about 14 weeks of gestation. Fetal pancreatic insulin secretion begins much later. Since maternal insulin does not cross the blood/placental barrier, other sources of insulin or insulin-like growth factors may be provided for fetal development. We report here that placental polyadenylylated RNAs from the first and third trimester of normal pregnancy as well as from term pregnancies of diabetic mothers hybridize to a 32P-labeled cloned cDNA of an insulin-related sequence expressed in fetal pancreas. Moreover, placentas from diabetic women express much more of these sequences. These results suggest that insulinrelated genes are expressed in placental tissue during fetal development and may be a source of growth-promoting hormones for the human fetus. Fetuses developing in diabetic women receive a large influx of glucose. This in turn may stimulate the expression of insulin-related sequences, which may result in higher utilization of glucose, thus bringing about the macrosomia and high incidence of malformation and stillbirths known to result from pregnancies in diabetics.During the first 10 weeks of embryonic and fetal life, which is a critical period of rapid growth for the human conceptus, primary and secondary embryonic induction and organogenesis is taking place (1). Glucose is used as a major source of metabolic energy in the human fetus (2-4) and a glucose imbalance, in addition to affecting the growth of embryonic tissue, may well result in developmental abnormalities such as macrosomia, malformations, and increased rate of stillbirths, as is manifested in pregnancies of diabetic women. Insulin, a regulator of glucose metabolism, is an essential growth factor for fast-growing mammalian tissues, including human embryonic tissues (2-4); however maternal insulin does not cross the blood/placental barrier (5-8). Although it has not been established that insulin or an insulin-like growth factor is necessary for the early development of the human fetus in utero, such a requirement is not unlikely.Explants of multiple tissues from fetal mouse synthesized insulin-like somatomedin (9). The production of the insulinlike growth factors IGF-I and IGF-II is developmentally regulated, and this pattern of expression is maintained in fibroblasts derived from fetal as well as older rats (10). Receptors for insulin-like growth factors (IGF-I, IGF-II, somatomedin A, and multiplication-stimulating activity) and insulin are present in human fetal tissues at different stages of development (11). This evidence suggests that fetal growth may be regulated by insulin and/or insulin-like growth factors.The fetal pancreatic islets of Langerhans are capable of insulin synthesis only after 14 weeks of gestation, several weeks later than the critical growth period mentioned above. Further, the fetal pancreas normally exhibits only limited responses to acute changes in cord blood gl...

show abstract

Glucagon metabolism in nonhuman primate pregnancy

Cited by 23 publications

References 14 publications

Fetal and Maternal Hormonal Response to Starvation in the Ewe

Fetal and Maternal Hormonal Response to Starvation in the Ewe

Release of glucose from the liver of fetal and postnatal sheep by portal vein infusion of catecholamines or glucagon.

Insulin-related genes expressed in human placenta from normal and diabetic pregnancies.

Contact Info

Product

Resources

About