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Biomedical subjects

E Herrera

Publications and source records attributed to E Herrera.

At least 145 records · Page 8Linked to original sources

Effects of exogenous insulin on placental transfer of maternal glucose to the rat fetus.

There is controversy concerning the possible modulation of glucose transfer to the fetus by insulin acting on the maternal side of the placenta. To study this question, 20.5 day pregnant rats were infused simultaneously with (U-14C)-D-glucose (via the jugular vein) and with different doses of insulin (via the left uterine artery) so that placentas from the left uterine horn were exposed to a higher insulin concentration than those from the right uterine horn. Placentas and fetuses from each uterine side were processed separately. No differences were detected in total blood radioactivity, plasma-14C-glucose, -14-C-lactate, -glucose, or -radioimmunoassayable insulin in fetuses from the left versus the right uterine horn. Total placenta radioactivity and 14C-glycogen were also similar in the left and right uterine sides at all insulin doses studied. Infusion of insulin (66 mU/min) to the pregnant rat caused hyperinsulinaemia and hypoglycaemia, decreased blood total radioactivity and plasma 14C-glucose, and increased plasma 14C-lactate in the mother. The level of fetal plasma 14C-glucose paralleled that of the mother. It is concluded that in the rat, placental glucose uptake, its transfer to the fetus, and fetal glucose utilization are not directly affected by maternal circulating insulin. Metabolic changes occurring in fetuses of hyperinsulinaemic mothers are secondary to the decreased availability of glucose.

Animals↗

Glucose infused through the portal vein enhances liver gluconeogenesis and glycogenesis from [3-14C]pyruvate in the starved rat.

After a pulse of [3-14C]pyruvate, 24 hr starved rats were infused through the portal vein with two different doses of glucose (7.8 or 20.8 mg/min) or the medium, and blood was collected from the inferior cava vein at the level of the suprahepatic veins. The highest dose of glucose enhanced the appearance of [14C]glucose in blood from the 2nd to the 20th min after tracer delivery. It also enhanced production of [14C]glycogen and concentration of glycogen in the liver after 5 and 20 min. At 20 min of glucose infusion the appearance of [14C]glyceride glycerol in liver as well as liver lactate concentration and lactate/pyruvate ratio were increased. The low dose of glucose used enhanced liver values of [14C]glycogen, [14C]glycogen specific activity and glycogen concentration. Our results support the hypothesis that in the starved rat glucose is converted into C3 units prior to being deposited as liver glycogen and based on the liver zonation model (Jungermann et al., 1983) it is proposed that glucose stimulated gluconeogenesis by shifting the liver to the cytosolic redox state as a secondary consequence of increased glycolytic activity.

Animals↗

Short-term insulin infused through the portal vein enhances liver gluconeogenesis and glycogenesis from [3-14C]pyruvate in the starved rat.

Insulin infusion through the portal vein immediately after a pulse of [3-14C]pyruvate in 24 hr starved rats enhanced the appearance of [14C]glucose at 2, 5 and 10 min and glucose specific activity at 1, 2 and 20 min in blood collected from the cava vein at the level of the suprahepatic veins. Insulin infusion for 5 min decreased liver pyruvate concentration and enhanced both liver and plasma lactate/pyruvate ratio, and it decreased the plasma concentration of all amino acids. When insulin was infused together with glucose, [14C]glucose levels and glucose specific activity decreased in blood but there was a marked increase in liver [14C]glycogen, glycogen specific activity and glycogen concentration, and an increase in liver lactate/pyruvate ratio. The effect of insulin plus glucose infusion on plasma amino acids concentration was smaller than that found with insulin alone. It is proposed that insulin effect enhancing liver gluconeogenesis is secondary to its effect either enhancing liver glycolysis which modifies the liver's cytoplasmic oxidoreduction state to its more reduced form, increasing liver amino acids consumption or both. In the presence of glucose, products of gluconeogenesis enhanced by insulin are diverted into glycogen synthesis rather than circulating glucose. This together with results of the preceding paper (Soley et al., 1985), indicates that glucose enhances liver glycogen synthesis from C3 units in the starved rat, the process being further enhanced in the presence of insulin.

Amino Acids↗

Similar metabolic response to acute ethanol intake in pregnant and non-pregnant rats either fed or fasted.

Plasma ethanol concentration 3 hr after its oral administration (3 g/kg body wt) did not differ in 20 day pregnant rats with virgin controls, and in both groups values were higher when studied after 24 hr fasted than when fed. In fed animals, blood glucose and liver glycogen concentrations were lower in pregnant than in virgin rats, whereas ethanol intake in both groups enhanced blood glucose levels, it reduced liver glycogen content only in virgins. In fetuses, maternal ethanol intake enhanced blood glucose levels. In fasted animals, ethanol intake decreased blood glucose levels in pregnant and virgin animals but did not affect these levels in fetuses. Ethanol intake enhanced beta-hydroxybutyrate/acetoacetate ratio similarly in blood of pregnant and virgin rats when either fed or fasted, and it produced the same change in fetuses from fasted mothers. Results indicate that the metabolic response to acute ethanol does not differ between pregnant and non-pregnant animals, and it is proposed that fetuses passively follow the metabolic changes occurring in their mothers after receiving ethanol.

3-Hydroxybutyric Acid↗

Decreased uterine blood flow in the diabetic pregnant rat does not modify the augmented glucose transfer to the fetus.

To determine whether changes in uterine blood flow affect placental glucose transfer in the diabetic pregnant rat, on the 7th day of gestation rats were intravenously treated with either streptozotocin (45 mg/kg) (diabetics) or buffer (controls). On the 20th day of gestation, fetal body weight and uterine blood flow appeared reduced whereas fetal/maternal plasma glucose was enhanced and lactate ratios were unchanged in diabetics versus controls. After 20 min of (U-14C)-D-glucose infusion through the maternal left uterine artery, plasma values of fetuses from left and right uterine horns were higher for 14C-glucose and lower for 14C-lactate in diabetics versus controls, and placental glucose transfer was greatly augmented in diabetics whether or not uterine blood flow was included in its calculation. Whereas a linear correlation existed between placental glucose transfer and maternal plasma glucose concentration, transferred glucose conversion into lactate remained stable even when the maternal glucose level was high. It was concluded that enhanced placental glucose transfer in the pregnant diabetic rat is not modified by reduced uterine blood flow. The limited capacity of the fetus to handle the great incoming flux of glucose through the placenta of a severely diabetic mother produces permanent hyperglycemia which may impair fetal growth.

Animals↗

Relationship between maternal and fetal fuels and placental glucose transfer in rats with maternal diabetes of varying severity.

Gestational diabetes mellitus (GDM) is a nonhomogeneous entity known to affect fetal development in different ways in both rats and human beings. The degree of severity of diabetes could affect the maternal-fetal transfer of metabolic fuels and consequently influence fetal development. To study this hypothesis, pregnant rats were made diabetic by streptozocin (STZ) treatment (45 mg/kg) at day 7 of gestation and were treated with different daily doses of insulin until the 20th day of gestation, when they were killed and examined. Differences in plasma glucose levels in the groups studied were not accompanied by differences in plasma glycerol, beta-hydroxybutyrate (beta-OHB), or total amino acid levels in mothers or their fetuses. Fetal/maternal ratios of these circulating fuels were not modified by maternal diabetes, whereas the glucose level was enhanced in diabetic rats not treated with insulin. Placental glucose transfer was studied directly with a recently reported in situ experimental design and was found to increase linearly with maternal glycemia, independently of whether this was modified by insulin treatment or by acute intravenous (i.v.) infusion of glucose in normal animals. Lactate production by the fetal/placental unit decreased in proportion to the glucose level in the maternal circulation. The present data indicate that the diabetic condition of the mother rat does not modify the mechanisms of placental transfer of metabolic fuels to the fetus, and that the actual transfer is mainly dependent on the concentrations of these fuels in the maternal circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

Effects of insulin on the utilization of 14C-glycerol and 14C-glucose in hepatectomized nephrectomized rats.

Insulin (i.v.) administration to functionally hepatectomized-nephrectomized rats did not alter circulating levels of glycerol and only slightly affected plasma radioactivity when animals received (U-14C)-glycerol, whereas after (U-14C)-glucose administration insulin enhanced hypoglycemia and greatly accelerated the rate of radioactivity loss from plasma. At 15 min after i.v. injection of (U-14C)-glycerol, radioactivity in total lipids was reduced in heart and lungs by insulin administration and enhanced in carcass and brown adipose tissue. These effects involved the 14C-glyceride glycerol fraction in the case of heart and 14C-fatty acids in carcass and adipose tissue. When (U-14C)-glucose was administered, insulin enhanced the appearance of 14C-water-soluble material in heart and carcass and 14C-total lipids in heart, carcass, and both brown and white adipose tissue. The effect in heart corresponded mainly to the 14C-glyceride glycerol fraction whereas it corresponded to the 14C-fatty acids in the other tissues. Therefore, insulin effects on glycerol metabolism substantially differ from those on glucose. Opposite effects on heart and lung glycerol utilization as compared to those in carcass and brown adipose tissue may account for the difficulties in observing changes in plasma glycerol levels after insulin treatment.

Adipose Tissue↗

The effect of streptozotocin diabetes on brain protein synthesis in the rat.

Young normal control rats were compared with a group made diabetic by treatment with streptozotocin and with other normal rats maintained on a restricted diet to obtain a daily body weight change similar to that of the diabetics. In diabetic rats plasma levels of Val, Ile and Leu rose and those of Asp, Thr, Ser, Gln, Gly, Tyr, Orn, Lys, His and Arg decreased, whereas brain concentrations of Leu, Arg and Orn were augmented and those of Thr and Ser reduced. Insulin treatment diminished these differences in comparison with controls values. In food-restricted normal rats plasma and brain amino acid concentrations also differed from values in normal controls but they were of different magnitude and/or direction than those of diabetics. In vitro 3H-Leucine incorporation into proteins by brain postmitochondrial dialyzed supernatants was unaffected in both diabetic and food-restricted rats, whereas in liver preparations the same parameter was significantly reduced in both groups and insulin treatment of the diabetics decreased this difference. Results indicate that brain amino acid concentrations in diabetic animals are a secondary consequence of their circulating levels and of potential modifications of brain amino acid metabolism other than protein synthesis, which is unaffected.

Amino Acids↗

Liver and kidney cortex gluconeogenesis from L-alanine in fed and starved rats.

Circulating [14C]glucose 2, 5 and 10 min after intravenous injection of [U-14C]-L-alanine was greater in 24 hr starved than in fed rats. In vitro uptake of [14C]alanine by liver and kidney cortex slices from 24 hr starved and fed rats rose in parallel with increased medium substrate concentration. Formation of [14C]glucose from 1mM [14C]alanine was similar in liver and kidney cortex slices and increased in tissues from 24 hr starved compared with fed rats. With 5 mM [14C]alanine more [14C]glucose was produced by liver than by kidney cortex slices from 24 hr starved rats. Liver slices always produced more [14C]lactate and less [14C]-CO2 from [14C]alanine than kidney cortex slices. It is proposed that under physiological conditions, the kidneys cortex actively participates in glucose production from alanine.

Alanine↗

Effects of anesthetics and starvation on in vivo gluconeogenesis in virgin and pregnant rats.

To study in vivo gluconeogenesis, female virgin rats were injected intravenously with 14C-alanine (ul) and the production of 14C-glucose was determined at two, five, or ten minutes thereafter. At ten minutes the appearance of 14C-glycogen in the liver was also determined. The intraperitoneal injection of sodium pentobarbital (Nembutal) (33 mg/kg body weight) 30 minutes prior the tracer did not affect the rate of gluconeogenesis in fed rats compared with unanesthetized animals, whereas in rats fasted 24 hours it produced a significant enhancement in all parameters studied. A similar effect in enhancing in vivo gluconeogenesis was observed with both pentobarbital or ether anesthesia when 3-14C-pyruvate was used as tracer in virgin rats fasted 24 hours. In contrast to the effect in virgin animals, pentobarbital anesthesia did not modify in vivo gluconeogenesis in either fed or 24-hour fasted 21-day pregnant rats. Ether anesthesia, however, caused an enhancement in 14C-glucose production from 3-14C-pyruvate in 24-hour fasted pregnant rats. On the basis of reported changes in sympathoadrenal activity produced by starvation and pregnancy, present results indicate that the enhancing effects of anesthetics on gluconeogenesis result from their capacity to stimulate adrenal medulla cathecholamine release or tissue sympathetic activity. Our findings also demonstrate that in an investigation of metabolic parameters it cannot be assumed that effects of anesthetics are always of the same degree and direction since they vary with the condition of the experimental subject.

Anesthetics↗

The effect of long-term ethanol maternal ingestion and withdrawal on brain regional monoamine and amino acid precursors in 15-day-old rats.

The effects of alcohol on brain monoamines were studied in 15-day-old offspring of rats given ethanol until the 21st day of gestation or the 15th day post partum. Increased noradrenaline concentrations were found in limbic system, hemispheres, diencephalon and brain stem of pups from mothers under alcohol treatment, and in hemispheres, diencephalon and brain stem of pups from deprived mothers. Serotonin and 5-hydroxyindol acetic acid were augmented in limbic system, diencephalon and brain stem of pups from mothers under alcohol whereas tyrosine was decreased in all brain regions studied in pups from alcoholic and deprived mothers. Consequently, chronic ethanol ingestion by pregnant rats has deleterious effects on CNS development of 15-day-old offspring which persists 15 days after alcohol withdrawal.

Alcoholism↗

[Intravenous sedation for gastroscopy: comparison between midazolam and diazepam].

Benzodiazepines are often used as premedication or intravenous sedative agents for endoscopies. The present study included 74 patients. It compared the sedative and amnestic properties of midazolam and diazepam, their relative potencies as well as the comfort of both the patient and the endoscopist during gastroscopy. The comparison has shown some statistically significant differences, allowing the following conclusions: amnesia was more frequent with midazolam; the dose requirement (in mg X kg-1) for adequate sedation was more important with diazepam, confirming the greater potency of midazolam; generally speaking, sedation was excellent with both drugs.

Adolescent↗

Selection of morphologically abnormal sperm by human cervical mucus.

The important role of cervical mucus from a reproduction standpoint is the transport and selection of spermatozoa. The study of the fertilizing ability of human spermatozoa by the use of zona-free hamster oocytes has shown that morphologically abnormal sperm can fuse with the zona-free hamster oocyte. The high proportion of morphologically abnormal spermatozoa present in human semen is significantly reduced after sperm migration through cervical mucus. The mucus, while a favorable environment for sperm survival, does not seem to contribute to the occurrence of sperm capacitation and acrosome reaction.

Animals↗

Changes with starvation in the rat of the lipoprotein lipase activity and hydrolysis of triacylglycerols from triacylglycerol-rich lipoproteins in adipose tissue preparations.

Lipoprotein lipase activity was higher in fat-pad pieces than in isolated adipocytes from the same fed rats, whereas hydrolysis of triacylglycerols from triacylglycerol-rich lipoproteins was similar in the two preparations when incubated either in basal conditions or in the presence of heparin. In both preparations there was a similar release of lipoprotein lipase activity into the medium during basal incubation, enhanced by the presence of heparin. In fat-pad pieces, but not in isolated adipocytes, incubation with heparin produced a decrease in the lipoprotein lipase activity measured in the tissue preparation. In fat-pad pieces from 24 h-starved rats, lipoprotein lipase activity was the same as in isolated adipocytes from the same animals and incubation with heparin did not affect the appearance of lipoprotein lipase in the medium or the utilization of triacylglycerols from triacylglycerol-rich lipoproteins. These results support the following conclusions. (1) The effectiveness of lipoprotein lipase in adipose tissue preparations in vitro depends more on its availability to the substrate than on its total activity. (2) Heparin acts on adipose tissue preparations from fed animals both by enhancing the release of pre-existing extracellular enzyme (which is absent in isolated adipocytes) and by enhancing the transfer outside the cells of the intracellular (and mainly undetectable) enzyme that is activated in the secretion process. (3) In adipose tissue from starved animals there is not only a decrease in the active extracellular form of lipoprotein lipase activity but also a reduction in the intracellular (and mainly undetectable) pool of the enzyme.

Adipose Tissue↗

Effects of insulin on the disposal of 14C-labelled very low density lipoprotein triglycerides in intact and hepatectomized rats.

In sham-operated rats, intravenous administration of 14C-very low density lipoprotein triglycerides (with labelled esterified fatty acids) caused an initial decrease and subsequent increase in plasma 14C-lipids of both very low density lipoproteins (VLDL) (density less than 1.006) and lipoproteins of density greater than 1.019. There was a similar change in 14C-lipids in adipose tissue and heart whereas in kidney, spleen and liver, 14C-lipids increased initially and then decreased. Insulin treatment in sham-operated animals decreased circulating 14C-lipids in VLDL and in lipoproteins of density greater than 1.019, while intermediate density (1.006-1.019) lipoproteins increased. Insulin also enhanced the radioactivity retained in spleen. In functionally hepatectomized rats, 14C-lipids progressively increased in heart. Insulin treatment in these rats enhanced the disappearance from circulation of 14C-VLDL and of lipoproteins of density greater than 1.019, as well as the appearance of 14C-intermediate density lipoproteins. The appearance of 14C-lipids in white adipose tissue also was augmented, while it decreased in heart and lung. Thus, in sham-operated animals, insulin apparently stimulates the uptake of products of VLDL metabolism by cells in the reticuloendothelial system, while in functionally hepatectomized rats there is increased heart utilization of VLDL triglycerides, and insulin enhances the net extrahepatic catabolism of these lipoproteins.

Adipose Tissue↗

Liver glucose, glycogen and lipid synthesis in fed and 24-hour fasted rats soon after a pulse of [3-14C]pyruvate through the portal vein.

1. A pulse of [3-14C]pyruvate was given to rats through the portal vein and blood was collected at brief intervals from the inferior cava vein at the level of the suprahepatic veins. 2. In 24 hr fasted rats, the appearance of [14C]glucose in blood and blood glucose specific radioactivity were higher than in fed animals from the first minute after delivery of the tracer. At this time total radioactivity did not differ between the two groups. 3. After 5 and 20 min. liver radioactivity present in glycogen and glyceride glycerol was enhanced while in fatty acids it was reduced in fasted as compared with fed animals. 4. It is proposed that, in the fasted state, both glycogen and glyceride glycerol synthesis are predominantly gluconeogenic processes.

Animals↗