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S U Devaskar

Publications and source records attributed to S U Devaskar.

At least 55 records · Page 3Linked to original sources
PubMed1992

Cellular localization and characterization of Glut 3 glucose transporter isoform in human brain.

In the present study we examined the expression and localization of Glut 3 in human brain using peptide-specific antisera. Glut 3 was expressed at 2-3 times higher levels in cerebral cortex from adult (n = 6) compared to that from neonatal infants (n = 4; P less than 0.05). However, similar levels of immunoreactive Glut 3 were present in cerebellum from adults (n = 6) and newborns (n = 4). Cellular localization of Glut 3 in adult (n = 5) and neonatal (n = 5) infant brains was undertaken by immunohistochemical analysis. Glut 3 was visible in the adult neuropil of the cerebral cortex; in certain cellular processes within the deeper cortical layers; in intravascular white cells, including monocytes, lymphocytes and granulocytes; and in microvascular endothelial cells. Neither the premature nor the mature newborn cerebral cortex exhibited Glut 3 labeling in the neuropil or microvasculature. In the cerebellum, given the stratified nature of the cellular arrangement, Glut 3 was more clearly and definitively noted in the cellular processes at all stages of development. Double labeling studies using neuronal (neurofilament) and astrocytic (glial fibrillary acidic protein) markers indicated that Glut 3 was primarily expressed in neurons. We conclude that Glut 3 is localized in many cellular components, including white blood cells in human brain. The prominent localization of Glut 3 to mature neuronal processes suggests an essential role for this transporter in regulating fuel requirements for dendritic and axonal traffic, thereby mediating neurotransmission. Further study is required to address the possibility that another as yet undefined glucose transporter isoform is expressed in other cell-specific regions of the brain.

Adult↗
PubMed1990

Insulin and insulin mRNA are detected in neuronal cell cultures maintained in an insulin-free/serum-free medium.

We investigated the effect of a serum-containing medium, exogenous insulin, and insulin-free/serum-free media in the regulation of the rabbit brain insulin-like peptide (ILP) in neuronal cell cultures. The presence of serum or insulin in the medium resulted in approximately 3-5% of neurons that were positive for the peptide by immunohistochemistry and for insulin mRNA by in situ hybridization. The absence of insulin in the medium resulted in a three- to fourfold increase (p less than 0.001) in the insulin-immunoreactive and insulin mRNA-containing neurons. Additionally, in the presence of exogenous insulin or serum, the amount of insulin present in the medium, as measured by ELISA, decreased with time (approximately 80%), the former slower than the latter when compared with their respective zero time point values. However, an increase (approximately 80% from zero time) was noted in the absence of insulin or serum, and this lasted for 24-48 hours alone. The presence of an increased insulin/ILP content in the medium and the increase in the numbers of insulin-immunoreactive neurons suggests an important role of the peptide in the brain. The observation of increased synthesis and secretion of neuronal ILP in the absence of insulin is indicative of an autocrine effect of exogenous insulin on neuronal production of ILP, which in turn may be important in the growth and maintenance of neuronal and possibly glial cells.

Animals↗
PubMed1987

The fetal heart insulin receptor responds differently to varying plasma insulin concentrations.

We investigated in vivo the effect of varying plasma concentrations of insulin on the 28- and 30-day-old fetal rabbit heart insulin receptors using plasma membranes. Alloxan induced maternal diabetes (n = 5) associated with fetal hyperglycemia and mild hyperinsulinemia (59.80 +/- 8.10 microU/ml versus a control of 26.25 +/- 3.70, p less than 0.01) increased the insulin receptor number from a control (30 d) of 168 +/- 1.01 to 320 +/- 34 X 10(10)/mg protein (p less than 0.01). Fetal administration of 1.0 U of insulin (n = 4) resulting in normoglycemia and moderately high plasma insulin concentrations (103.3 +/- 34.63 microU/ml versus a control of 13.72 +/- 1.60, p less than 0.05) did not alter the insulin receptor number (28 d). On the other hand fetal administration of 2.0 U of insulin (n = 4) resulting in hypoglycemia and severely high plasma insulin concentrations (288.3 +/- 51 microU/ml versus a control of 13.72 +/- 1.60, p less than 0.01) decreased the insulin receptor number from a control (28 d) of 200 +/- 23 to 82 +/- 23 X 10(10)/mg protein (p less than 0.01). The receptor affinity remained constant. We conclude that the downregulation (decrease) of the fetal heart insulin receptors in vivo is not a physiologic but a pharmacologic effect of insulin.

Animals↗
PubMed1986

Varying brain insulin concentrations differentially regulate the fetal brain insulin receptor.

We investigated the downregulating effect of varying states (physiologic and pharmacologic) of systemic and intracranial hyperinsulinism on the 28 to 30 day fetal rabbit brain insulin receptor. Alloxan-induced maternal diabetes (n = 5) produced mild fetal hyperinsulinemia (D) (plasma insulin concentrations = 59.80 +/- 8.10 microU/ml, control = 26.25 +/- 3.70; p less than 0.01), whereas systemic administration (IMI) of 1.0 U (n = 4) and 2.0 U (n = 4) of insulin to the fetus resulted in moderate (103.13 +/- 34.63 microU/ml) and severe (288.3 +/- 51 microU/ml) fetal hyperinsulinemia respectively. All three states of systemic hyperinsulinemia neither altered the fetal brain insulin content nor the brain insulin receptor number and affinity. 0.01 U (n = 4) of intracranial insulin administration (ICI) increased the brain insulin content four-fold (p less than 0.01) but did not alter the brain insulin receptor number or affinity. 0.1 (n = 5) and 2.0 U (n = 7) of intracranial insulin increased the brain insulin content to supraphysiologic concentrations (p less than 0.01) and decreased the fetal brain insulin receptor number (p less than 0.01), the affinity remaining constant. We conclude that 1) regardless of the ability of insulin to cross the blood brain barrier, the downregulation of the brain insulin receptor is insulin dose-dependent and 2) the downregulation of the fetal brain insulin receptor is not a physiologic but a pharmacologic effect of insulin.

Animals↗
PubMed1986

Acute bronchospasm resembling status asthmaticus during the neonatal period.

Recently, we encountered four neonates who developed severe reversible partial lower airway obstruction. This communication describes their clinical course and the pathogenesis and treatment of acute bronchospasm resembling status asthmaticus and leading to life-threatening respiratory acidosis.

Acidosis, Respiratory↗
PubMed1986

Ontogenesis of the insulin receptor in the rabbit brain.

We delineated the ontogeny of the brain insulin binding, insulin receptor number and affinity using plasma membranes isolated from the rabbit. Specific 125I-insulin binding and receptor number expressed per milligram of protein increased from the 20 day gestation fetus to the 1-day-old newborn, declining thereafter to attain adult values by day 6 of postnatal life. Specific 125I-insulin binding and the receptor number in the adult brain was less than the fetal and neonatal (1 day) brain receptors. Although a similar trend was observed specifically during fetal development, the changes in receptor number expressed per microgram DNA were not significant in the neonatal period. The adult brain insulin receptor number was higher than the 20- to 27-day fetus and similar to that of the 30-day fetus and the 1- to 5-day newborns. The total receptor number correlated linearly with the brain plasma membrane protein increment velocity. The affinity of the receptors increased during early fetal development (20-27 days) and remained constant thereafter in the postnatal period. We conclude that the ontogenic changes of the brain insulin receptors are similar to the ontogenic changes of brain plasma membrane protein. The developmental changes are more pronounced when the receptor number is expressed per milligram protein versus microgram DNA.

Animals↗
PubMed1986

Ontogeny of plasma-free thyroxine and triiodothyronine concentrations during the perinatal period and maternofetal transfer of thyroid hormones in the rabbit.

Although rabbit has been used as a convenient animal model in understanding the role of thyroid hormones during the perinatal development, ontogenetic changes in plasma-free thyroxine or triiodothyronine concentration has not been studied in this species. We delineated the ontogeny of immunoreactive plasma-free thyroxine and triiodothyronine concentration during the perinatal period. It is generally believed that thyroid hormones do not cross the placenta from the mother to the fetus in sufficient concentrations to exert biological effects in the fetus. We administered 250 micrograms/kg of thyroxine (T4) or 125 micrograms/kg of triiodothyronine (T3) intramuscularly to the rabbit doe on the 25th and 26th day of gestation. Maternal and fetal plasma-free T4, T3 and glucose concentration and fetal liver glycogen content were quantitated on the 27th day of gestation. Maternal and fetal plasma-free T4 and T3 concentration was significantly higher than the control in T4-treated animals. Maternal and fetal plasma T3 concentration was higher and free T4 concentration lower than the control in T3-treated animals. T3 or T4 treatment resulted in fetal hyperglycemia and depletion of fetal hepatic glycogen content. We conclude that T4 or T3 cross the rabbit placenta and exert thyromimetic effects in the fetus. A convenient animal model to investigate in utero effects of T4 or T3 in mammalian fetal development is proposed.

Animals↗
PubMed1986

Regulation of neonatal heart glycogen metabolism by thyroxine.

We investigated the effect of hyperthyroidism and hypothyroidism on the myocardial glycogen metabolism by quantitating 125I-insulin binding, glycogen content, glycogen synthase and phosphorylase enzyme activities in the newborn rabbit. Although an increase in 125I-insulin binding was observed in response to hyperthyroidism (p less than 0.01), a decrease in myocardial glycogen (p less than 0.01) along with no change in the synthase and phosphorylase enzyme activity was demonstrated. On the other hand, propylthiouracil-induced hypothyroxinemia did not affect the 125I-insulin binding, glycogen content or the two enzyme systems. We conclude that the depletion of myocardial glycogen secondary to hyperthyroidism is independent of an increase in 125I-insulin binding or any change in the major glycogen enzyme activities (synthase and phosphorylase). We speculate that this decline in neonatal heart glycogen may be secondary to thyroxine-induced altered glucose uptake or modified postinsulin receptor events.

Animals↗
PubMed1986

Altered thyroidal states modulate the insulin receptor characteristics of the developing rabbit brain.

We investigated the effect of propylthiouracil (PTU)-induced hypothyroidism and T4-induced hyperthyroidism on the fetal and neonatal rabbit brain insulin receptors (number and affinity) using plasma membranes. PTU administration to the pregnant mothers resulted in low serum-free T4 and normal total T3 concentrations, while T4 therapy to the mothers resulted in high serum-free T4 and high total T3 concentrations in the fetus and neonate. PTU-induced hypothyroidism did not affect the fetal brain insulin receptors, cholesterol content (brain homogenate) or protein content. On the other hand, brain insulin receptor number and total brain cholesterol content decreased in the neonate. T4 therapy at 100 micrograms/kg reversed the serum T4 to the control value and normalized the neonatal brain insulin receptor number and cholesterol content while a higher dose of T4 (200 micrograms/kg) increased the neonatal brain insulin receptor number, cholesterol and protein content. We conclude that altered thyroidal states modulate the brain insulin receptor (number and affinity) in neonatal, but not fetal brain plasma membranes.

Animals↗
PubMed1985

Internalization of the neonatal brain insulin receptor.

Using 10-15 day neonatal rabbit brain cells, we studied the internalization (n = 6) and intracellular degradation (n = 8) of specifically bound 125I-insulin. In addition we investigated the association between the internalization of the specifically bound 125I-insulin and the metabolic effects of insulin such as glucose (n = 13) and amino-acid (leucine) uptake (n = 6). Phenylarsine oxide (10 microM), an agent that inhibits the internalization of the insulin receptor (n = 6) decreased the specifically bound 125I-insulin in the intact and trypsin-resistant (inside) part of the brain cells by 50% (p less than 0.05). On the other hand chloroquine (100 microM), a lysosomotropic agent that interferes with the intracellular degradation of the insulin receptor (n = 8) increased two-fold the 125I-insulin specifically bound to the intact and trypsin resistant part of the cells (p less than 0.05). Both these agents did not alter the time-dependent basal glucose uptake by the brain cells. Glucose alone regulated its own uptake (n = 4) whereas 1 X 10(-6) M insulin did not augment the glucose uptake (n = 11+13) above basal. Similarly leucine regulated the leucine uptake (n = 4) but insulin did not alter this basal uptake by the brain cells (n = 6). In summary we observed no associated glucose or leucine uptake along with the presence of internalization and intracellular degradation of specifically bound 125I-insulin in the brain cells.

Amino Acids↗
PubMed1985

Inulin space studies in fetal sheep.

Extracellular volume was estimated in fetal sheep by measuring the 14C inulin space in 6 in situ unanesthetized fetal lambs at gestational ages ranging from 120 to 145 days (term = 150 days). The total inulin space ranged from 979 to 1,510 ml. A positive correlation between total inulin space and gestational age (r = 0.65) was noted, such that fetal lambs of 120 days gestation had a predicted inulin space of 1,072 ml and fetal lambs near term at 145 days gestation had an inulin space of 1,422 ml. However, since fetal weight increases with gestation, inulin space expressed as a percent of body weight actually decreased with gestational age (r = -0.80), so that at 120 days gestation the fetus would have an estimated inulin space of 59% of body weight and at 145 days the fetus would have an inulin space of only 34% of body weight.

Animals↗
PubMed1985

Thyroid-dependent maturation of neonatal brain but not lung epidermal growth factor receptors.

Although the role of thyroid hormones in enhancing lung and brain maturation during the perinatal period is well established, the cellular mechanisms involved in these processes are incompletely understood. Hypothyroidism retards the development of fetal pulmonary insulin, neonatal pulmonary beta-adrenergic and neonatal brain insulin receptors. In this study, we investigated the effect of hypo- or hyperthyroidism on the development of neonatal brain and lung epidermal growth factor (EGF) receptors. The rabbit pups were rendered hypothyroid by adding 0.05% propylthiouracil to the drinking water starting at 23 days of gestation and thereafter. The neonatal hyperthyroid state was achieved by intramuscular administration of 100 micrograms/kg of synthroid to the rabbit doe on the 29th and 30th day of pregnancy. Neonatal plasma free thyroxine (T4) concentrations were quantitated by a radioimmunoassay. Brain and lung plasma membranes were isolated by differential centrifugation. EGF receptor characteristics were studied using 125I-EGF binding assays and Scatchard analysis. The plasma free T4 concentrations were 0.36 +/- (SEM) 0.02 (n = 6), p less than 0.01 (n = 7) and 1.76 +/- 0.1 (n = 6) ng/dl in the control, hypothyroid and hyperthyroid pups, respectively. The percent specific binding of 125I-EGF to 200 micrograms of brain plasma membrane (BPM) protein was significantly lower in the hypothyroid (0.62 +/- 0.03, n = 7, p less than 0.01), and higher in the thyroxine-treated (1.58 +/- 0.08, n = 6, p less than 0.01) group when compared to control (1.08 +/- 0.06, n = 6) animals. However, the percent specific binding of 125I-EGF to 100 micrograms of lung plasma membrane (LPM) protein was similar in all three groups (2.24 +/- 0.28, control; 2.01 +/- 0.5, hypothyroid, and 2.26 +/- 0.3, hyperthyroid). The number of EGF receptors per milligram of BPM protein (X 10(-10] were lower in the hypothyroid (2.24 +/- 0.03, n = 5) and higher in the hyperthyroid (6.6 +/- 0.02, n = 4) group when compared to control (4.4 +/- 0.05, n = 4) with no apparent difference in Kd. There was no difference in the number of EGF binding sites per milligram of LPM protein (X 10(-10] within the groups (6.6 +/- 0.8, n = 6, control; 7.9 +/- 0.4, n = 4, hypothyroid, and 7.3 +/- 0.3, n = 4, hyperthyroid). Presence of high affinity receptors for EGF in the neonatal brain as well as lung supports the hypothesis that EGF may play an important role in neonatal brain and lung maturation.(ABSTRACT TRUNCATED AT 400 WORDS)

5'-Nucleotidase↗
PubMed1985

A differential effect of thyroxine and glucocorticoids on fetal brain and heart insulin receptor.

We investigated the effect of thyroxine (T4), glucocorticoids, and T4 + glucocorticoids on the maturation of fetal rabbit brain and heart insulin receptors. Five doses of T4 over 10 days (50 micrograms/kg body weight per dose) were administered to the mother; significant amounts crossed the placenta (fetal serum free T4 = 0.75 +/- 0.08 versus a control of 0.21 +/- 0.02 ng/dl, p less than 0.02) and increased the specific binding of [125I]insulin to 30-day-old fetal heart membranes from a control of 3.6 +/- 0.74% per 100 micrograms protein to 5.8 +/- 0.19% (p less than 0.05). Curvilinear Scatchard plots revealed an increase in receptor number X 10(7) micrograms protein-1 from 137 +/- 4 to 244 +/- 39 (p less than 0.05) with no change in receptor affinity. No appreciable alteration by T4 in the [125I]insulin-specific binding and receptor number of 30-day fetal brains was noted. Fetal heart glycogen content was decreased and there was a small increase in plasma glucose concentration in the T4-treated group (each p less than 0.02). Betamethasone at 0.17 mg/kg did not affect the specific binding of [125I]insulin to 27-day fetal heart or brain plasma membranes, although a decrease in heart glycogen content and an increase in plasma glucose concentration were observed (each p less than 0.02). Also T4 + betamethasone did not alter the [125I]insulin binding to 27-day fetal heart or brain plasma membranes, but resulted in an additive effect (a marked depletion) on cardiac glycogen (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Insulin downregulates neonatal brain insulin receptors.

Insulin (2U-regular) was administered intracerebrally or intraperitoneally in newborn rabbit pups, to study the effect of the hormone on brain insulin receptor characteristics. Intraperitoneal insulin treatment produced an increase in plasma insulin concentrations from a control of approximately 24 microU/ml to 132 +/- 36 (p less than 0.02) and a decrease in plasma glucose from approximately 83 to 27 +/- 10 mg/dl (p less than 0.01). No change in brain insulin receptor characteristics was observed. On the other hand, insulin injected intracerebrally raised the plasma insulin to greater than 3000 microU/ml and lowered the plasma glucose to 32 +/- 8 mg/dl (p less than .05). In addition a decrease in brain insulin receptor sites from 262 +/- 9 X 10(10) mg protein-1 to 159 +/- 6 (p less than 0.001) was noted. When the data was expressed per microgram DNA, a decrease from 4 +/- 0.4 X 10(10) to 2.5 +/- 0.2 (p less than .01) in receptor sites resulted. No change in the receptor affinity was observed. We conclude that a direct exposure of the brain to excess insulin results in a down-regulation of the brain insulin receptors.

Animals↗
PubMed1984

Glucagon and glucose dynamics in sheep: evidence for glucagon resistance in the fetus.

We compared the effects of glucagon infused at 5 and 50 ng X kg-1 X min-1 on glucose turnover (GT), production (Ra), and utilization (Rd) in the fetal (F; n = 5, gestation 129 +/- 3 days, term approximately 150 days) and nonpregnant adult (A; n = 5 and 6) sheep. Infusion of glucagon at 5 ng X kg-1 X min-1 raised fetal glucagon levels (IRG) from a basal of 168 +/- 27 to a mean sustained level of 863 +/- 160 pg/ml but had no effect on basal levels of glucose (G) of 12 +/- 3 mg/dl, insulin (IRI) of 16 +/- 3 microU/ml, GT of 21 +/- 1.3 mg/min, and Rd of 15 +/- 2 mg/min; Ra remained negligible. When fetal IRG was raised to a mean sustained level of 1,809 +/- 210 pg/ml by infusion of glucagon at 50 ng X kg-1 X min-1, G doubled to 23 +/- 1.5 mg/dl, IRI rose to 21 +/- 0.9 microU/ml, GT rose to 60 +/- 5 mg/min, Rd to 30 +/- 4.8 mg/min, and Ra to 41 +/- 6 mg/min (P less than 0.01 for each) indicating induction of F glucose production so that GT was now derived from endogenous sources. By contrast, when IRG levels were raised from 109 +/- 10 to 538 +/- 43 pg/ml by infusion of 5 ng X kg-1 X min-1 to A, basal G rose from 56 +/- 2 to 88 +/- 6 mg/dl, IRI from 24 +/- 2 to 45 +/- 6 microU/ml, GT and Ra from 93 +/- 7 to 173 +/- 17 mg/min, and Rd from 93 +/- 7 to 148 +/- 12 mg/min (P less than 0.01 for each). No further increments of these indexes occurred in A when IRG was raised to a mean sustained level of 2,275 +/- 135 pg/ml by infusion of 50 ng X kg-1 X min-1. These results indicate a relative resistance in F to the glycemic effects of glucagon, consistent with previously demonstrated decreases of hepatic glucagon receptors and glucagon-stimulated cAMP production in fetal liver.

Animals↗
PubMed1984

25-hydroxy- and 1 alpha,25-dihydroxyvitamin D. Maternal-fetal relationship and the transfer of 1,25-dihydroxyvitamin D3 across the placenta in an ovine model.

Plasma concentrations of 25-hydroxy- and 1,25-dihydroxyvitamin D in chronically catheterized fetal and maternal sheep preparations and transfer of 3H-1,25-(OH)2-D3 from the fetus to mother and vice versa were studied. We tested the hypothesis that 1,25-(OH)2-D does not cross the placenta in either direction. While the fetal plasma 25-(OH)-D concentration was lower than the corresponding maternal values (n = 9, p less than 0.02), the fetal 1,25-(OH)2-D concentration was higher than the mother's (n = 9, p less than 0.02). 3H-1,25-(OH)2-D3 crossed the placenta from the fetus to the mother (n = 4) and vice versa (n = 4). We speculate, therefore, that maternal vitamin D metabolism may be affected by fetal vitamin D metabolism through the transplacental crossover of its highly active metabolite.

Animals↗