Insulin-Glucagon Substrate Interrelations in the Fetal Sheep

Abstract

Extract METHODS AND MATERIALSTwenty-four studies were conducted in 14 sheep fetuses to Fourteen healthy date-bred pregnant ewes with gestational investigate the pancreatic islet a! and /3 cell responses to ages ranging from 100-145 days were studied. The chronic substrate infusions. The studies were conducted between 100 indwelling catheter preparation was utilized and has been days gestation and near term, using indwelling vascular described previously (14). Briefly, a laparotomy through a left catheters for infusions and blood sampling. constant glucose flank incision was performed using spinal anesthesia and infusions (6 mg/kg/min) produced a significant rise in the aseptic technique. Either a jugular vein and carotid artery or a mean concentration of insulin in plasma by 105 min, but no femoral vein and artery were isolated and catheterized, change in glucagon in plasma was observed. Near term (>I35 depending on whether the fetal head or hind limb was most days) the mean plasma insulin increment with constant glucose conveniently exposed. Following catheter placement, the fetus infusion was significantly greater and occurred sooner than in was returned to the uterine cavity and the laparotomy closed.fetuses early in gestation (<I10 days), but again no plasma The catheters were exteriorized, marked, and secured on the glucagon response was observed. The mean steady state mother's back. The ewes usually began to ambulate with 6-8 glucose concentration in response to the 6 mg/kg/min glucose hr after surgery. Antibiotics (Ampicillin, 2 g intramuscularly, infusion was similar early and late in gestation, even though and Kanamycin, 0.5 g intramuscularly) were administered the steady state plasma level of insulin in plasma was higher in daily for 5 days. Studies were performed 3-6 days postsurthe late gestation fetuses. Alanine infused into the fetus did gery, at which time maternal dietary intake had returned to not alter concentrations of glucose, insulin, or glucagon in normal and fetal blood gases and pH had stabilized within plasma, These data suggest that changes in plasma concentralimits.tions of insulin and glucagon are not important in the One group of eight animals received 2-hr constant infusions regulation of substrate metabolism during fetal!ife. Moreover, (6 mg/kg/min) by of a Holter 'Onstant the pancreatic islet /3 cell secretion response seems to mature infusion Pump. In another group of six animals, a similar earlier than the a cell response.glucose infusion protocol was used, but at the end of 90 min the infusion rate was doubled to 12 mg/kg/min and continued for another 90 min. In two animals a continuous infusion of Speculation saline was given at similar rates over the same time period. ~h~ failure of glucagon to respond to alanine Blood was drawn at.15-min intervals throughout the infusion during fetal life suggests immaturity of glucagon control of periods for blood glucose measurement and at specified time gluconeogenesis from amino acids. The low levels of activity of intervals (OJ 457 752 ...

Effects of Exogenous Glucagon on Concentrations of Glucose, Fructose and Insulin in Plasma of Sheep Fetus

“…Ep stein et al [12] found no increase in fetal glu cagon in the rhesus monkey made glucose intolerant with streptozotocin. Similar obser vations have been made in the fetal lamb, in which the concentration failed to change in response to fetal glucose infusion [15], In studies of chronic maternal fasting in the ewe, we found no significant change in the concentration of glucagon in fetal plasma during short-term fasting [37], but did find a trend towards an increased glucagon concen tration with a prolonged fast (more than 6 days) [36]. The purpose of this study was to investigate the effect of exogenous glucagon on fetal glucose, fructose and insulin in the sheep.…”

“…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 [10,15]. Chez et al [10] have shown that fetal hypo glycemia.…”

Fetal and Maternal Hormonal Response to Starvation in the Ewe

“…Epstein et al (10) found no increase in fetal glucagon in the rhesus monkey made glucoseintolerant with streptozotocin. Fiser et al (12) as in monkey and man is significantly less than in the maternal blood. The data in this study would suggest that glucagon is not an important regulator of fetal metabolism during maternal starvation because there was no significant change in the glucagon concentration in the fetus throughout the study.…”

Metabolic and Hormonal Response to Chronic Maternal Fasting in the Ewe

“…Epstein et al (7) found no increase in fetal glucagon in the rhesus monkey made glucose intolerant with streptozotocin. Fiser et al (11) found no in crease in glucagon concentration in response to glucose infusion in the fetus. The concen tration of glucagon in the fetal sheep, as well as in monkey and man.…”