scholarly journals Spatial control of neuronal metabolism through glucose-mediated mitochondrial transport regulation

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Anamika Agrawal ◽  
Gulcin Pekkurnaz ◽  
Elena F Koslover
Keyword(s):  
Spatial Organization ◽  
Metabolic Response ◽  
Limited Range ◽  
Projection Neurons ◽  
Glucose Levels ◽  
Energy Demands ◽  
Consumption Rates ◽  
Mitochondrial Distribution ◽  
Organelle Trafficking ◽  
Spatially Varying

Eukaryotic cells modulate their metabolism by organizing metabolic components in response to varying nutrient availability and energy demands. In rat axons, mitochondria respond to glucose levels by halting active transport in high glucose regions. We employ quantitative modeling to explore physical limits on spatial organization of mitochondria and localized metabolic enhancement through regulated stopping of processive motion. We delineate the role of key parameters, including cellular glucose uptake and consumption rates, that are expected to modulate mitochondrial distribution and metabolic response in spatially varying glucose conditions. Our estimates indicate that physiological brain glucose levels fall within the limited range necessary for metabolic enhancement. Hence mitochondrial localization is shown to be a plausible regulatory mechanism for neuronal metabolic flexibility in the presence of spatially heterogeneous glucose, as may occur in long processes of projection neurons. These findings provide a framework for the control of cellular bioenergetics through organelle trafficking.

scholarly journals Spatial Control of Neuronal Metabolism Through Glucose-Mediated Mitochondrial Transport Regulation

2018 ◽  
Author(s):  
Anamika Agrawal ◽  
Gulcin Pekkurnaz ◽  
Elena F. Koslover
Keyword(s):  
Spatial Organization ◽  
Metabolic Response ◽  
Limited Range ◽  
Glucose Levels ◽  
Energy Demands ◽  
Neuronal Metabolism ◽  
Consumption Rates ◽  
Mitochondrial Distribution ◽  
Spatially Varying

Eukaryotic cells modulate their metabolism by organizing metabolic components in response to varying nutrient availability and energy demands. In the axons of mammalian neurons, mitochondria have been shown to respond to glucose levels by halting active transport preferentially in high glucose regions. Here, we employ quantitative modeling to explore the physical limits on spatial organization of organelles through such regulated stopping of processive motion, as well as the consequences to cellular metabolism. We delineate the role of key parameters, including cellular glucose uptake and consumption rates, that are expected to modulate mitochondrial distribution and metabolic response in spatially varying glucose conditions. Our quantitative estimates indicate that physiological brain glucose levels fall within the limited range necessary for metabolic enhancement, making this a plausible regulatory mechanism for neuronal metabolic flexibility in the presence of spatially heterogeneous glucose. These findings highlight the role of spatial organization in the regulation of neuronal metabolism, while providing a quantitative framework for the establishment of such organization by control of organelle trafficking.

scholarly journals INFORM: INFrared-based ORganizational Measurements of tumor and its microenvironment to predict patient survival

2021 ◽  
Vol 7 (6) ◽  
pp. eabb8292
Author(s):  
Saumya Tiwari ◽  
Andre Kajdacsy-Balla ◽  
Joshua Whiteley ◽  
Georgina Cheng ◽  
Stephen M. Hewitt ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Spatial Organization ◽  
Infrared Imaging ◽  
Patient Survival ◽  
High Definition ◽  
Risk Of Death ◽  
Measurement Framework ◽  
Spatially Varying ◽  
Physical And Chemical

The structure and organization of a tumor and its microenvironment are often associated with cancer outcomes due to spatially varying molecular composition and signaling. A persistent challenge is to use this physical and chemical spatial organization to understand cancer progression. Here, we present a high-definition infrared imaging–based organizational measurement framework (INFORM) that leverages intrinsic chemical contrast of tissue to label unique components of the tumor and its microenvironment. Using objective and automated computational methods, further, we determine organization characteristics important for prediction. We show that the tumor spatial organization assessed with this framework is predictive of overall survival in colon cancer that adds to capability from clinical variables such as stage and grade, approximately doubling the risk of death in high-risk individuals. Our results open an all-digital avenue for measuring and studying the association between tumor spatial organization and disease progression.

scholarly journals Experience affects exercise-induced changes in catecholamines, glucose, and FFA

1989 ◽  
Vol 256 (1) ◽  
pp. R169-R173 ◽  
Author(s):  
A. J. Scheurink ◽  
A. B. Steffens ◽  
G. H. Dreteler ◽  
L. Benthem ◽  
R. Bruntink
Keyword(s):  
Metabolic Response ◽  
Plasma Catecholamines ◽  
Plasma Free Fatty Acid ◽  
Blood Component ◽  
Experimental Conditions ◽  
Glucose Levels ◽  
Exercise Induced ◽  
Induced Changes ◽  
Response To Exercise ◽  
First Time

The interference of the experimental conditions on the exercise-induced alterations in plasma catecholamines, plasma free fatty acids, and glucose and insulin concentrations was investigated in rats. Exercise consisted of strenuous swimming against a countercurrent (0.22 m/s) for 15 min in a pool with water of 33 degrees C. Before, during, and after swimming, blood samples were taken through a permanent heart catheter. The blood component levels in rats that were confronted with exercise for the very first time were compared with the levels in rats that were well accustomed to the exercise conditions. The very first time rats swam caused an enhanced release of epinephrine from the adrenal medulla and a reduced output of norepinephrine from the sympathetic nerve endings. Furthermore, in the first time swim group, blood glucose levels were higher and plasma free fatty acid concentrations were lower compared with the well-accustomed animals. There were no differences in plasma insulin concentrations. It is concluded that the experimental conditions may interfere considerably with the hormonal and metabolic response to exercise. Furthermore the results reinforce the idea that the two parts of the sympathoadrenal system are functionally and metabolically dissociated.

scholarly journals Acute effects of hydrocortisone on the metabolic response to a glucose load: increase in the first-phase insulin secretion

2010 ◽  
Vol 163 (2) ◽  
pp. 225-231 ◽  
Author(s):  
Greisa Vila ◽  
Michael Krebs ◽  
Michaela Riedl ◽  
Sabina M Baumgartner-Parzer ◽  
Martin Clodi ◽  
...  
Keyword(s):  
Science Studies ◽  
Cell Function ◽  
Metabolic Response ◽  
Peptide Yy ◽  
Β Cell ◽  
C Peptide ◽  
Glucose Levels ◽  
Load Increase ◽  
Β Cell Function ◽  
First Phase Insulin Secretion

Background and aimSeveral basic science studies support the existence of non-genomic glucocorticoid signaling in pancreas, liver, and adipocytes, but its clinical relevance has not yet been elucidated. This study aimed at investigating the rapid effects of hydrocortisone on the human metabolic response to glucose.Subjects and methodsIn a randomized placebo-controlled crossover study, ten healthy men received an i.v. bolus of 0.6 mg/kg hydrocortisone once and placebo once 4 min before the administration of 330 mg/kg glucose. Cortisol, glucose, insulin, C-peptide, ghrelin, and peptide YY (PYY) levels were measured during the following 3 h. Minimal model analysis was performed for evaluating the metabolic response.ResultsHydrocortisone attenuated the rise in plasma glucose during the initial 15 min following glucose administration (P=0.039), and it led to lower glucose levels during the first 2 h (P=0.017). This was accompanied by enhanced circulating insulin (P=0.02) and C-peptide (P=0.03) levels during the initial 15 min, and a 35% increase in the first-phase β-cell function (P=0.003). Hydrocortisone decreased PYY concentrations during the initial 30 min (P=0.014), but it did not affect the ghrelin response to glucose.ConclusionOne i.v. bolus of hydrocortisone induces rapid effects on carbohydrate metabolism increasing the first-phase β-cell function. The modulation of PYY plasma levels suggests the possible non-genomic effects of glucocorticoids on appetite-regulatory hormones.

scholarly journals Metabolic and endocrine response to exercise: sympathoadrenal integration with skeletal muscle

2014 ◽  
Vol 224 (2) ◽  
pp. R79-R95 ◽  
Author(s):  
Derek Ball
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Pathways ◽  
Metabolic Response ◽  
Contractile Activity ◽  
Substrate Availability ◽  
Sympathoadrenal System ◽  
Endocrine Response ◽  
Energy Demands ◽  
Current Review ◽  
Response To Exercise

Skeletal muscle has the capacity to increase energy turnover by ∼1000 times its resting rate when contracting at the maximum force/power output. Since ATP is not stored in any appreciable quantity, the muscle requires a coordinated metabolic response to maintain an adequate supply of ATP to sustain contractile activity. The integration of intracellular metabolic pathways is dependent upon the cross-bridge cycling rate of myosin and actin, substrate availability and the accumulation of metabolic byproducts, all of which can influence the maintenance of contractile activity or result in the onset of fatigue. In addition, the mobilisation of extracellular substrates is dependent upon the integration of both the autonomic nervous system and endocrine systems to coordinate an increase in both carbohydrate and fat availability. The current review examines the evidence for skeletal muscle to generate power over short and long durations and discusses the metabolic response to sustain these processes. The review also considers the endocrine response from the perspective of the sympathoadrenal system to integrate extracellular substrate availability with the increased energy demands made by contracting skeletal muscle. Finally, the review briefly discusses the evidence that muscle acts in an endocrine manner during exercise and what role this might play in mobilising extracellular substrates to augment the effects of the sympathoadrenal system.

Liver energy metabolism during hibernation in the golden-mantled ground squirrel, Spermophilus lateralis

1997 ◽  
Vol 75 (7) ◽  
pp. 1059-1065 ◽  
Author(s):  
James F. Staples ◽  
Peter W. Hochachka
Keyword(s):  
Ground Squirrels ◽  
Atp Production ◽  
Spermophilus Lateralis ◽  
Energy Demands ◽  
Hormone Status ◽  
Consumption Rates ◽  
Lower Temperature ◽  
Production Capacities ◽  
Deep Hibernation ◽  
Normothermic Condition

Large changes in ATP production capacities and rates have been reported in mammalian hibernators throughout the different stages of the hibernation cycle. In this study we showed that total extractable liver [ATP], [ADP], and [ATP]/[ADP] do not differ among summer normothermic, hibernating, and aroused golden-mantled ground squirrels, Spermophilus lateralis, indicating that metabolism remains well balanced throughout the hibernation cycle. This implies that rates of ATP consumption must be down-regulated during deep hibernation in order to maintain this balance. Despite this, basal oxygen-consumption rates [Formula: see text] of hepatocytes isolated from hibernating, aroused, and summer cold-acclimated ground squirrels were 22.4–35.1% higher than those from ground squirrels in the summer normothermic condition when measured at 37 °C. The relatively high hepatocyte [Formula: see text] may help to minimize interbout arousal times, reducing energy demands during the hibernation season. At 7 °C, hepatocyte [Formula: see text] values do not differ among the four groups; however, the Q10 for hepatocyte [Formula: see text] is significantly lower for the summer group, suggesting lower temperature sensitivity. Despite the seasonal changes in thyroid hormone status known to occur in scuirid hibernators, the proportion of hepatocyte [Formula: see text] attributed to Na+,K+-ATPase, estimated by inhibition with 1 mM ouabain, is only around 15% and does not differ among hibernation/seasonal conditions.

scholarly journals Adrenal glands are essential for activation of glucogenesis during undernutrition in fetal sheep near term

2011 ◽  
Vol 300 (1) ◽  
pp. E94-E102 ◽  
Author(s):  
A. L. Fowden ◽  
A. J. Forhead
Keyword(s):  
Adrenal Glands ◽  
Metabolic Response ◽  
Glucose Production ◽  
Oxygen Metabolism ◽  
In Utero ◽  
Endogenous Glucose Production ◽  
Hepatic Glycogen ◽  
Fetal Sheep ◽  
Glucose Levels ◽  
Near Term

In adults, the adrenal glands are essential for the metabolic response to stress, but little is known about their role in fetal metabolism. This study examined the effects of adrenalectomizing fetal sheep on glucose and oxygen metabolism in utero in fed conditions and after maternal fasting for 48 h near term. Fetal adrenalectomy (AX) had little effect on the rates of glucose and oxygen metabolism by the fetus or uteroplacental tissues in fed conditions. Endogenous glucose production was negligible in both AX and intact, sham-operated fetuses in fed conditions. Maternal fasting reduced fetal glucose levels and umbilical glucose uptake in both groups of fetuses to a similar extent but activated glucose production only in the intact fetuses. The lack of fasting-induced glucogenesis in AX fetuses was accompanied by falls in fetal glucose ultilization and oxygen consumption not seen in intact controls. The circulating concentrations of cortisol and total catecholamines, and the hepatic glycogen content and activities of key gluconeogenic enzymes, were also less in AX than intact fetuses in fasted animals. Insulin concentrations were also lower in AX than intact fetuses in both nutritional states. Maternal glucose utilization and its distribution between the fetal, uteroplacental, and nonuterine maternal tissues were unaffected by fetal AX in both nutritional states. Ovine fetal adrenal glands, therefore, have little effect on basal rates of fetal glucose and oxygen metabolism but are essential for activating fetal glucogenesis in response to maternal fasting. They may also be involved in regulating insulin sensitivity in utero.

Physiological and metabolic response to isolated closed-head injury

1987 ◽  
Vol 66 (3) ◽  
pp. 388-395 ◽  
Author(s):  
Clifford Scott Deutschman ◽  
Frank N. Konstantinides ◽  
Sandra Raup ◽  
Frank B. Cerra
Keyword(s):  
Head Injury ◽  
Metabolic Response ◽  
Closed Head Injury ◽  
Large Data ◽  
Nitrogen Excretion ◽  
Content Type ◽  
Steroid Administration ◽  
Glucose Levels ◽  
Closed Head ◽  
Metabolic Indices

✓ In order to determine the effects of steroid administration on the metabolic response to isolated closed-head injury, a longitudinal study was performed. Metabolic indices were prospectively evaluated for the first 5 days postinjury in six patients who received steroids and 10 patients who did not. Patients were carefully screened to eliminate those with associated injuries as well as those with abnormalities due to sepsis. Other than steroid administration, a uniform treatment regimen was used in both groups. Metabolic indices measured on postinjury Days 1, 3, and 5 were analyzed. In addition, data were compared to results in large data banks obtained both from overnight-fasted patients (fasted controls) and from polytrauma victims (stressed controls). Both treatment groups were comparable with respect to age, mean Glasgow Coma Scale scores on admission and on Day 5, and initial intracranial pressure. Metabolic data indicated significantly higher levels of nitrogen excretion and somatic protein mobilization in steroid-treated patients than in patients not receiving steroids. In both groups, glucose levels, the lactate/pyruvate ratio, and branched-chain amino acid levels (all metabolic indices that correlate well with level of stress) initially corresponded to values for stressed controls. By Day 5, values for these variables were similar to fasted controls for the group not receiving steroids. In patients receiving steroids, however, the data remained similar to those for stressed controls. It is concluded that steroids prolong the metabolic abnormalities associated with the initial phase of head injury. In view of inconclusive data regarding benefit from steroid administration, serious questions must be raised regarding the use of these catabolic agents in this setting.

Using n-alkane markers to estimate forage intake of mule deer

2006 ◽  
Vol 84 (11) ◽  
pp. 1576-1583 ◽  
Author(s):  
G.W. Kuzyk ◽  
R.J. Hudson
Keyword(s):  
Mule Deer ◽  
Critical Factor ◽  
Odocoileus Hemionus ◽  
East Central ◽  
Energy Demands ◽  
Carbon Chains ◽  
Aspen Parkland ◽  
Consumption Rates ◽  
Forage Intake ◽  
Free Ranging

Dry matter intake (DMI) of free-ranging mule deer ( Odocoileus hemionus (Rafinesque, 1817)) in the aspen parkland of east-central Alberta was estimated using the double n-alkane ratio and bite count methods. Eleven female mule deer were given an intraruminal capsule containing synthetic n-alkanes and released into 4–8 ha paddocks. Known concentration of even-chained carbon (C32) was released from the capsules and recovered 7–10 days later from freshly voided faeces. Odd carbon chains of adjacent length (C31:C33) were extracted from vegetation samples gathered during behavioural observations of four tame deer. Calculations from the pairings (C31:C32; C33:C32) provided estimates of DMI that ranged from 1.29 to 2.73 kg/day. DMI was highest during autumn, possibly to prepare for increased energy demands for the upcoming winter. No differences were found in seasonal or annual comparisons of bite rates, but bite sizes differed in all comparisons, suggesting bite size was a critical factor affecting consumption rates for mule deer on northern ranges. Maximum bite sizes rose from 49 ± 5 mg/bite in July to 213 ± 58 mg/bite in October. Maximum consumption rates were in October of both years (3.6–4.4 g/min) and occasionally approached theoretical maxima (14.3–15.6 g/min).

Analysis of intracellular oxygenation of isolated adult cardiac myocytes

1986 ◽  
Vol 250 (3) ◽  
pp. C384-C390 ◽  
Author(s):  
D. P. Jones ◽  
F. G. Kennedy
Keyword(s):  
Diffusion Coefficient ◽  
Cardiac Myocyte ◽  
Heart Cells ◽  
O2 Consumption ◽  
Intracellular Diffusion ◽  
Consumption Rates ◽  
Mitochondrial Distribution ◽  
The Difference ◽  
O2 Supply ◽  
Function Relationship

The influence of cellular shape, cellular O2 consumption rate, and intracellular diffusion coefficient for O2 on the magnitude of intracellular O2 gradients during hypoxia was analyzed with the model of Boag (Curr. Top. Radiat. Res. 5: 141-195, 1969) to determine whether these parameters could account for the experimentally measured O2 dependence curves for myoglobin (Mb) oxygenation and cytochrome a + a3 oxidation in heart cells. The analysis shows that the intracellular diffusion coefficient for O2 must be below 4 X 10(-6) cm2/s for a substantial intracellular gradient to occur. The intracellular diffusion coefficient was calculated from the difference in half-maximal oxidation (P50) values for isolated Mb and intracellular Mb and was found to be 1.76 X 10(-6) cm2/s. Use of this value and appropriate geometric models satisfactorily described the O2 dependence of Mb oxygenation and cytochrome a + a3 oxidation in cells over an eightfold range of O2 consumption rates. However, the analysis does not account for the correspondence of intracellular P50 values of Mb oxygenation and cytochrome a + a3 oxidation. This implies that there exists an intracellular heterogeneity of either Mb distribution, mitochondrial distribution, or mitochondrial respiratory characteristics. Such heterogeneity would further contribute to diffusion limitation of O2 supply during hypoxia and could be a major factor underlying the cardiac myocyte structure-function relationship.

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