Hyperglycemia and hyperinsulinemia increase glucose utilization in fetal rat tissues

1987 ◽  
Vol 253 (6) ◽  
pp. E616-E620
Author(s):  
A. Leturque ◽  
J. P. Revelli ◽  
S. Hauguel ◽  
J. Kande ◽  
J. Girard
Keyword(s):  
Glucose Utilization ◽  
Fetal Heart ◽  
Blood Glucose Concentration ◽  
Insulin Level ◽  
Rat Tissues ◽  
Exogenous Insulin ◽  
Fetal Tissues ◽  
Hindlimb Muscles ◽  
Metabolic Index ◽  
The Brain

In vivo measurement of glucose utilization by individual tissues of 19-day rat fetuses have been performed using radioactive 2-deoxy-D-glucose technique. In the basal state, glucose metabolic index was 13.6 +/- 0.5 ng.min-1.mg-1 for the whole fetus, 21 +/- 1 in the hindlimb muscles, 13 +/- 2 in the liver, and 16 +/- 2 in the brain, whereas the fetal heart had the highest value: 62 +/- 5 ng.min-1.mg-1. To raise the fetal glycemia, the basal maternal blood glucose concentration of 0.78 +/- 0.02 g/l was elevated to 1.04 +/- 0.02 g/l by mean of hyperglycemic clamps. The fetal hyperglycemia increased glucose metabolic index by 30-100% over basal values in all the tissues tested except in the brain. To raise fetal insulinemia, maternal euglycemic clamp with supraphysiological insulin concentrations were performed, then a fraction (1%) of exogenous insulin crossed the placenta. Fetal plasma insulin concentrations were thus elevated to 180 +/- 32 and 255 +/- 23 microU/ml. The fetal heart increased significantly its glucose metabolic index in response to the lower insulin level. Glucose metabolic index in hindlimb muscles and liver was increased by 50-100% for the highest insulin level, whereas the brain was unaffected by exogenous insulin. We conclude that glucose metabolic index is stimulated by physiological hyperglycemia in individual fetal tissues and that fetal tissues (heart, liver, and muscle) are sensitive to exogenous insulin.

Fetal glucose utilization in response to maternal starvation and acute hyperketonemia

1989 ◽  
Vol 256 (6) ◽  
pp. E699-E703 ◽  
Author(s):  
A. Leturque ◽  
S. Hauguel ◽  
J. P. Revelli ◽  
A. F. Burnol ◽  
J. Kande ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Ketone Body ◽  
Glucose Utilization ◽  
Fetal Liver ◽  
Rat Tissues ◽  
Pregnant Rats ◽  
Hindlimb Muscles ◽  
Decrease Blood Glucose ◽  
Beta Hydroxybutyrate

The effects of maternal hypoglycemia and/or hyperketonemia on glucose utilization by individual fetal rat tissues have been studied in vivo. To decrease blood glucose and to raise fetal blood ketone body concentrations, 19-day pregnant rats were submitted to 48 or 96 h of starvation. To differentiate between the effects of decreased blood glucose and increased ketone body concentrations, fed pregnant rats were infused for 2 h with DL-beta-hydroxybutyrate. After 96 h of maternal starvation, fetal 2-deoxy-D-glucose (2DG) uptake decreased from 13.6 +/- 0.5 to 8.6 +/- 1.15 micrograms.min-1.g-1. This was mainly due to a decrease in 2DG uptake by fetal hindlimb muscles and heart. By contrast, 2DG uptake in fetal liver and brain was not affected by maternal starvation. Acute hyperketonemia in fed pregnant rats induced a 23% decrease in 2DG uptake by the whole fetus mainly as the result of a lowered 2DG uptake in fetal hindlimb muscles. These data suggest that fetal 2DG uptake does not simply depend on lowered blood glucose level during maternal starvation but that other hormonal, cardiovascular, or metabolic adaptations are implicated. In the rat, most of the fetal tissues including brain are protected against maternal hypoglycemia.

scholarly journals Fetal hypoxia and apoptosis following maternal porcine reproductive and respiratory syndrome virus (PRRSV) infection

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Carolina M. Malgarin ◽  
Fiona Moser ◽  
J. Alex Pasternak ◽  
Glenn Hamonic ◽  
Susan E. Detmer ◽  
...  
Keyword(s):  
Viral Load ◽  
Strong Evidence ◽  
Fetal Death ◽  
Fetal Heart ◽  
High Viral Load ◽  
Group Differences ◽  
Respiratory Syndrome Virus ◽  
Third Trimester ◽  
Fetal Tissues ◽  
The Brain

Abstract Background Mechanisms of fetal death following maternal PRRSV2 infection remain uncharacterized, although hypoxia from umbilical cord lesions and/or placental detachment due to apoptosis are hypothesized. We performed two experiments examining hypoxia and apoptosis in PRRSV-infected and non-infected, third-trimester fetuses to elucidate possible associations with fetal death. Fetuses were selected based on four phenotypic infection groups: fetuses from non-challenged control gilts (CTRL); low viral load fetuses (LVL; Exp 1) or uninfected fetuses (UNINF; Exp 2) from inoculated gilts; viable high viral load fetuses (HVL-VIA); and HVL meconium-stained fetuses (HVL-MEC). Results In experiment 1, paraffin embedded fetal tissues collected 21 days post maternal infection (DPI) were examined for DNA fragmentation associated with apoptosis. Positively stained foci were larger and more numerous (P < 0.05) in heart, liver, and thymus of HVL-VIA and HVL-MEC compared to CTRL and LVL fetuses. In experiment 2, group differences in gene expression within the hypoxia (HIF1a, IDO1, VEGFa, LDHA, NOS2, NOX1) and apoptosis (CASP3, CASP7, CASP8, CASP9, RIPK1, RIPK3) pathways were assessed by RT-qPCR in fetal tissues collected at 12 DPI. High viral load fetuses showed differential expression relative to the CTRL and UNINF (P < 0.05 for all). Brain tissue from HVL-VIA and HVL-MEC fetuses presented increased expression of CASP7, CASP8, RIPK3, HIF1a and IDO1. Fetal heart showed increased expression of CASP8, HIF1a, IDO and NOX1 and a decrease in NOS2 expression in infected groups. CASP7, CASP9, RIPK1 and RIPK3 were only increased in the heart of HVL-VIA while VEGFa was only increased for HVL-MEC fetuses. Thymus from HVL-MEC had decreased expression of CASP9 and there was increased IDO1 in all infected fetuses. Conclusions There is strong evidence of apoptosis occurring in the heart, liver and thymus of highly viral load fetuses at 21 DPI. Furthermore, there was clear upregulation of apoptotic genes in the heart of high viral load infected fetuses and less prominent upregulation in the brain of PRRSV-infected fetuses, whereas thymus appears to be spared at 12 DPI. There was no strong evidence of hypoxia at 12 DPI in brain and thymus but some indication of hypoxia occurring in fetal heart.

Insulin secretion and substrate homeostasis in prolonged hypothermia in rats

1988 ◽  
Vol 255 (6) ◽  
pp. R1035-R1040
Author(s):  
R. Hoo-Paris ◽  
M. L. Jourdan ◽  
L. C. Wang ◽  
R. Rajotte
Keyword(s):  
Insulin Secretion ◽  
Plasma Glucose ◽  
Low Temperatures ◽  
Plasma Insulin ◽  
Glucose Utilization ◽  
Exogenous Insulin ◽  
Metabolic Substrate ◽  
Endogenous Insulin ◽  
Dose Dependent Decrease ◽  
Dose Dependent

In hypothermia, impairment of metabolic substrate mobilization and utilization may be a factor limiting survival. By use of a newly developed technique, substrate profiles and their regulation by insulin were examined in hypothermic rats (body temperature 19 degrees C) over 24 h. Plasma glucose concentrations increased to approximately 300 mg/dl during cooling and remained high throughout the period of hypothermia. Free fatty acid (FFA) concentration was not altered during cooling or during the first 10 h of hypothermia (approximately 700 mu eq/l) but progressively decreased thereafter, reaching 420 mu eq/l by 20 h. Plasma insulin decreased dramatically during cooling and remained very low (9 +/- 2 microU/ml) during the whole period of hypothermia, reflecting the suppression of insulin secretion by isolated islets at low temperatures. To test he hypothesis that suppression of endogenous insulin secretion may hamper glucose utilization and thus limit survival in hypothermia, exogenous insulin was administered. At doses of 0.1, 0.5, and 1 U/kg intravenously, insulin slowly decreased plasma glucose and FFA. However, at 0.1 and 1 U/kg intraperitoneally, insulin resulted in a dose-dependent decrease in survival time in the hypothermic rat. It is possible that the antilipolytic effect of insulin may have outweighed any beneficial effect of improving glucose utilization in hypothermia.

Development of the Biostator Glucose clamping algorithm.

1982 ◽  
Vol 28 (9) ◽  
pp. 1899-1904 ◽  
Author(s):  
A H Clemens ◽  
D L Hough ◽  
P A D'Orazio
Keyword(s):  
Animal Studies ◽  
Insulin Infusion ◽  
Blood Glucose Concentration ◽  
Human Subjects ◽  
Pancreatic Beta Cell ◽  
Model System ◽  
Exogenous Insulin ◽  
Maturity Onset Diabetes ◽  
Beta Cell Response ◽  
Infusion System

Abstract The "glucose clamping" technique has been proposed as a method for the early detection of a beginning derangement of glucose homeostasis and thus for the possible prevention of maturity-onset diabetes. This technique interrupts the physiological glucose-insulin relationship by placing a patient's blood glucose concentration under an investigator's control, for quantification of the pancreatic beta-cell response during hyperglycemic clamps and of sensitivity of body tissue to exogenous insulin during normoglycemic clamps. We report the development of a glucose clamping algorithm for use with the Biostator glucose-controlled insulin-infusion system (Horm. Metab. Res., Suppl. 8: 23-33, 1977). This algorithm adds simplicity and precision to the glucose clamping procedure and reduces operator effort to a minimum. We describe the early development of the algorithm with a model system and report evaluations made during animal studies and preliminary investigations with human subjects.

scholarly journals Biosynthesis of anandamide and N-palmitoylethanolamine by sequential actions of phospholipase A2 and lysophospholipase D

2004 ◽  
Vol 380 (3) ◽  
pp. 749-756 ◽  
Author(s):  
Yong-Xin SUN ◽  
Kazuhito TSUBOI ◽  
Yasuo OKAMOTO ◽  
Takeharu TONAI ◽  
Makoto MURAKAMI ◽  
...  
Keyword(s):  
Biosynthetic Pathway ◽  
Brain Homogenate ◽  
Wide Distribution ◽  
Rat Tissues ◽  
Lysophospholipase D ◽  
Pla2 Enzyme ◽  
First Time ◽  
Hydrolysis Of ◽  
The Brain

Anandamide (an endocannabinoid) and other bioactive long-chain NAEs (N-acylethanolamines) are formed by direct release from N-acyl-PE (N-acyl-phosphatidylethanolamine) by a PLD (phospholipase D). However, the possible presence of a two-step pathway from N-acyl-PE has also been suggested previously, which comprises (1) the hydrolysis of N-acyl-PE to N-acyl-lysoPE by PLA1/PLA2 enzyme(s) and (2) the release of NAEs from N-acyllysoPE by lysoPLD (lysophospholipase D) enzyme(s). In the present study we report for the first time the characterization of enzymes responsible for this pathway. The PLA1/PLA2 activity for N-palmitoyl-PE was found in various rat tissues, with the highest activity in the stomach. This stomach enzyme was identified as group IB sPLA2 (secretory PLA2), and its product was determined as N-acyl-1-acyl-lysoPE. Recombinant group IB, IIA and V of sPLA2s were also active with N-palmitoyl-PE, whereas group X sPLA2 and cytosolic PLA2α were inactive. In addition, we found wide distribution of lysoPLD activity generating N-palmitoylethanolamine from N-palmitoyl-lysoPE in rat tissues, with higher activities in the brain and testis. Based on several lines of enzymological evidence, the lysoPLD enzyme could be distinct from the known N-acyl-PE-hydrolysing PLD. sPLA2-IB dose dependently enhanced the production of N-palmitoylethanolamine from N-palmitoyl-PE in the brain homogenate showing the lysoPLD activity. N-Arachidonoyl-PE and N-arachidonoyl-lysoPE as anandamide precursors were also good substrates of sPLA2-IB and the lysoPLD respectively. These results suggest that the sequential actions of PLA2 and lysoPLD may constitute another biosynthetic pathway for NAEs, including anandamide.

scholarly journals C60 Fullerene Prevents Restraint Stress-Induced Oxidative Disorders in Rat Tissues: Possible Involvement of the Nrf2/ARE-Antioxidant Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Olga O. Gonchar ◽  
Andriy V. Maznychenko ◽  
Nataliya V. Bulgakova ◽  
Inna V. Vereshchaka ◽  
Tomasz Tomiak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Protein Expression ◽  
Restraint Stress ◽  
Stress Condition ◽  
Rat Tissues ◽  
Stress Exposure ◽  
The Brain ◽  
Nrf2 Protein

The effects of C60FAS (50 and 500 μg/kg) supplementation, in a normal physiological state and after restraint stress exposure, on prooxidant/antioxidant balance in rat tissues were explored and compared with the effects of the known exogenous antioxidant N-acetylcysteine. Oxidative stress biomarkers (ROS, O2⋅−, H2O2, and lipid peroxidation) and indices of antioxidant status (MnSOD, catalase, GPx, GST, γ-GCL, GR activities, and GSH level) were measured in the brain and the heart. In addition, protein expression of Nrf2 in the nuclear and cytosol fractions as well as the protein level of antiradical enzyme MnSOD and GSH-related enzymes γ-GCLC, GPx, and GSTP as downstream targets of Nrf2 was evaluated by western blot analysis. Under a stress condition, C60FAS attenuates ROS generation and O2⋅− and H2O2 releases and thus decreases lipid peroxidation as well as increases rat tissue antioxidant capacity. We have shown that C60FAS supplementation has dose-dependent and tissue-specific effects. C60FAS strengthened the antiradical defense through the upregulation of MnSOD in brain cells and maintained MnSOD protein content at the control level in the myocardium. Moreover, C60FAS enhanced the GSH level and the activity/protein expression of GSH-related enzymes. Correlation of these changes with Nrf2 protein content suggests that under stress exposure, along with other mechanisms, the Nrf2/ARE-antioxidant pathway may be involved in regulation of glutathione homeostasis. In our study, in an in vivo model, when C60FAS (50 and 500 μg/kg) was applied alone, no significant changes in Nrf2 protein expression as well as in activity/protein levels of MnSOD and GSH-related enzymes in both tissues types were observed. All these facts allow us to assume that in the in vivo model, C60FAS affects on the brain and heart endogenous antioxidative statuses only during the oxidative stress condition.

Expression of vascular permeability factor/vascular endothelial growth factor in normal rat tissues

1993 ◽  
Vol 264 (4) ◽  
pp. C995-C1002 ◽  
Author(s):  
W. T. Monacci ◽  
M. J. Merrill ◽  
E. H. Oldfield
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
In Situ Hybridization ◽  
Rat Tissues ◽  
Vascular Endothelial ◽  
Vascular Permeability Factor ◽  
Organ Specific ◽  
Normal Rat ◽  
Endothelial Growth Factor ◽  
The Brain

Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is a approximately 43-kDa secreted protein that has been shown in bioassays to induce endothelial proliferation, angiogenesis, and capillary hyperpermeability. VPF has been suggested to play an important role in the physiology of normal vasculature. To further elucidate the natural functions of VPF in vivo, the expression of VPF in normal tissues was examined using Northern blot analysis and in situ hybridization histochemistry. VPF mRNA is expressed in the brain, kidney, liver, lung, and spleen of the healthy adult rat. On Northern blots, the relative abundance of VPF mRNA observed in these tissues was highest in the lung and lowest in the spleen. As determined by in situ hybridization, the patterns of VPF expression are organ specific. Hybridization of an antisense VPF probe was concentrated in the cerebellar granule cell layer of the brain and in the glomeruli and tubules of the kidney. In the liver and lung, intense hybridization was observed homogeneously throughout both tissues, demonstrating that VPF mRNA is present in virtually every hepatocyte and pulmonary alveolar cell. Hybridization to the spleen was weaker and more diffuse. The widespread expression and organ-specific distribution of VPF mRNA in normal rat tissues supports the suggestion of an extensive role for this factor in the physiology of normal vasculature.

scholarly journals Cloning, Characterization, and Expression Features of Chicken CDS2 Splicing Variants

2020 ◽  
Author(s):  
Yuanyuan Xu ◽  
Shuping Zhang ◽  
Yujun Guo ◽  
Wen Chen ◽  
Yanqun Huang
Keyword(s):  
Adipose Tissue ◽  
Real Time ◽  
Real Time Pcr ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Exogenous Insulin ◽  
Quantitative Real Time Pcr ◽  
Temporal Expression ◽  
Spatio Temporal ◽  
The Brain

Abstract Background: The CDS gene encodes the CDP-diacylglycerol synthase enzyme that catalyzes the formation of CDP-diacylglycerol (CDP-DAG) from phosphatidic acid. At present, there are no reports of CDS2 in birds. Here, we identified chicken CDS2 transcripts by combining conventional RT- PCR amplification, 5' RACE (Fig. 1A), and 3' RACE, explored the spatio-temporal expression profiles of total CDS2 and the longest transcript variant CDS2-4, and investigated the effect of exogenous insulin on total the mRNA level of CDS2 by quantitative real-time PCR. Results: Four transcripts of chicken CDS2 (CDS2-1, -2, -3, and -4) were identified, which were alternatively spliced at the 3′-untranslated region (UTR). CDS2 was widely expressed in all tissues examined and the longest variant CDS2-4 was the major transcript. Both total CDS2 and CDS2-4 were prominently expressed in adipose tissue and the heart, and exhibited low expression in the liver and pectoralis of 49 day-old chickens. Quantitative real-time PCR revealed that total CDS2 and CDS2-4 had different spatio-temporal expression patterns in chicken. Total CDS2 exhibited a similar temporal expression tendency with a high level in the later period of incubation (embryonic day 19 [E19] or 1-day-old) in the brain, liver, and pectoralis. While CDS2-4 presented a distinct temporal expression pattern in these tissues, CDS2-4 levels peaked at 21 days in the brain and pectoralis, while liver CDS2-4 mRNA levels were highest at the early stage of hatching (E10). Total CDS2 (P < 0.001) and CDS2-4 (P = 0.0090) mRNA levels in the liver were differentially regulated throughout development of the chicken. Exogenous insulin significantly downregulated the level of total CDS2 at 240 min in the pectoralis of Silky chickens (P < 0.01). Total CDS2 levels in the liver of Silky chickens were higher than that of the broiler in the basal state and after insulin stimulation. Conclusion: Chicken CDS2 has multiple transcripts with variation at the 3′-UTR, which was prominently expressed in adipose tissue. Total CDS2 and CDS2-4 presented distinct spatio-temporal expression patterns, and they were differentially regulated with age in liver. Insulin could regulate chicken CDS2 levels in a breed- and tissue-specific manner.

scholarly journals The Influence of Biological and Technical Factors on the Variability of Global and Regional Brain Metabolism of 2-[18F]Fluoro-2-Deoxy-D-Glucose

1992 ◽  
Vol 12 (2) ◽  
pp. 281-290 ◽  
Author(s):  
Edwaldo E. Camargo ◽  
Zsolt Szabo ◽  
Jonathan M. Links ◽  
Samuel Sostre ◽  
Robert F. Dannals ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Concentration ◽  
Temporal Cortex ◽  
Peak Time ◽  
Operational Equation ◽  
Complex Functions ◽  
Coefficients Of Variations ◽  
Technical Factors ◽  
The Individual ◽  
The Brain

This study investigated the influence of biological and technical factors on variations of global and regional cerebral metabolic rate of glucose (CMRglc) measured with 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG). Twelve male volunteers (22–40 years) were investigated on three or four occasions for a total of 42 studies. We calculated the variance/covariance of the following parameters: CMRglc, six parameters of the blood clearance of [18F]FDG, hour of injection, peak time of blood radioactivity, and six components of the operational equation (nonradioactive blood glucose concentration, brain radioactivity, two integrals, numerator, and denominator). There was correlation among these six components, except for nonradioactive blood glucose. However, the correlation between the CMRglc and the individual components of the operational equation was poor. The inter- and intrapersonal CMRglc coefficients of variations were 13.8 and 7.1%, respectively. In contrast, coefficients of variations of the numerator and denominator of the operational equation were 34.6 and 32.6%, respectively, and were always in the same direction. No correlation was found between CMRglc and the technical factors in the numerator and denominator of the operational equation. Factor analysis disclosed that a single factor was responsible for 70% of the variance. This factor included caudate, putamen, thalamus, frontal cortex, temporal cortex, and cingulate gyrus. These structures are involved with multiple complex functions, from autonomic motor control to behavior and emotions. The intrinsic metabolic variability of these structures, along with the basal metabolic processes that are continuously going on in the brain, may be the best explanation for the variance encountered in our investigation.

Hypoglycaemia in the treatment of diabetes mellitus

2011 ◽  
pp. 1849-1861
Author(s):  
Pratik Choudhary ◽  
Stephanie A. Amiel
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Blood Glucose Concentration ◽  
Cerebral Metabolism ◽  
Chronic Complications ◽  
Glucose Levels ◽  
Patients With Diabetes ◽  
Treatment Of Diabetes ◽  
Clinically Significant ◽  
The Brain

Hypoglycaemia (low blood glucose concentration) is the most important acute complication of the pharmacological treatment of diabetes mellitus. Low blood glucose impairs brain (and, potentially, cardiac) function. The brain has minimal endogenous stores of energy, with small amounts of glycogen in astroglial cells. The brain is therefore largely dependent on circulating glucose as the substrate to fuel cerebral metabolism and support cognitive performance. If blood glucose levels fall sufficiently, cognitive dysfunction is inevitable. In health, efficient glucose sensing and counterregulatory mechanisms exist to prevent clinically significant hypoglycaemia. These are impaired by diabetes and by its therapies. Patients with diabetes rank fear of hypoglycaemia as highly as fear of chronic complications such as nephropathy or retinopathy (1). Fear of hypoglycaemia, hypoglycaemia itself and attempts to avoid hypoglycaemia limit the degree to which glycaemic control can be intensified to reduce the risk of chronic complications of diabetes both for type 1 and type 2 diabetes.

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