Rates of glucose utilization in brain of active and hibernating ground squirrels

1995 ◽  
Vol 268 (2) ◽  
pp. R445-R453 ◽  
Author(s):  
K. U. Frerichs ◽  
G. A. Dienel ◽  
N. F. Cruz ◽  
L. Sokoloff ◽  
J. M. Hallenbeck
Keyword(s):  
Glucose Utilization ◽  
Specific Activity ◽  
Ground Squirrels ◽  
Cold Adapted ◽  
Precursor Pool ◽  
Glucose Levels ◽  
Operational Equation ◽  
Dg Method ◽  
Deep Hibernation ◽  
Cerebral Structures

Rates of glucose utilization (CMRGlc) were determined in some cerebral structures of active warm- and cold-adapted ground squirrels and hibernating ground squirrels with [14C]deoxyglucose (DG) by direct chemical measurement of precursor and products in samples dissected from funnel-frozen brain. The rate of supply relative to demand of glucose and [14C]DG in brain of hibernating animals was similar to or greater than that of controls. [14C]DG cleared from the plasma in hibernators much more slowly than in active animals, and the level of unmetabolized [14C]DG in brain and the integrated specific activity of the precursor pool in plasma exceeded those of the active animals by 4- to 10-fold. At 45 min after an intravenous pulse of [14C]DG, the unmetabolized [14C]DG remaining in the brains of the hibernators accounted for approximately 96% of the total 14C compared with approximately 10-15% in the active animals. The value of lambda, a factor contained in the lumped constant of the operational equation of the [14C]DG method, was estimated for each animal and found to be relatively constant over the sixfold range of glucose levels in the brains of all animals. Calculated CMRGlc in squirrels in deep hibernation was only 1-2% of the values in active animals.

scholarly journals Brain Glucose Levels in Portacaval-Shunted Rats with Chronic, Moderate Hyperammonemia: Implications for Determination of Local Cerebral Glucose Utilization

1994 ◽  
Vol 14 (1) ◽  
pp. 113-124 ◽  
Author(s):  
Nancy F. Cruz ◽  
Gerald A. Dienel
Keyword(s):  
Glucose Utilization ◽  
Normal Values ◽  
Brain Structures ◽  
Glucose Content ◽  
Brain Glucose ◽  
Glucose Levels ◽  
Lumped Constant ◽  
Dg Method ◽  
The Brain

Rates of glucose utilization (lCMRglc) in many structures of the brain of fed, portacaval-shunted rats, when assayed with the [14C]deoxyglucose (DG) method in our laboratory, were previously found to be unchanged (30 of 36 structures) or depressed (6 structures) during the first 4 weeks after shunting, but to rise progressively to higher than normal values in 25 of 36 structures from 4–12 weeks. In contrast, lCMRglc, when assayed with the [14C]glucose method in another laboratory, was depressed in most structures of brains of 4–8-week shunted rats that had relatively high brain ammonia levels. There was a possibility that the increases in lCMRglc obtained with the [14C]DG method may have been artifactual, due, in part, to a change in brain glucose content which could alter the value of the lumped constant of the DG method. Brain glucose levels of shunted rats were, therefore, assayed by both direct chemical measurement in freeze-blown samples and by determination of steady-state brain:plasma distribution ratios for [14C]methylglucose; the methylglucose distribution ratio varies as a function of plasma and tissue glucose contents. Within a week after shunting, ammonia levels in blood and brain rose to 0.25–0.30 m M and 0.35–0.70 μmol/g, respectively, and mean plasma glucose levels fell from 9–10 m M to 7.4–8.5 m M, and then remained nearly constant. Brains of fedshunted rats had normal glycogen levels and stable but moderately reduced glucose contents between 1 and 12 weeks (i.e., 1.9–2.2 μmol/g). [14C]Methylglucose distribution ratios were essentially the same as those in controls in 22 brain structures at 2 and 8 weeks after shunting. Because brain glucose levels remained stable from 1 to 12 weeks after shunting, there is no evidence to support the hypothesis that the value of the lumped constant would have changed and caused an artifactual rise in lCMRglc.

Blood glucose replacement rates in normal and diabetic humans

1961 ◽  
Vol 16 (5) ◽  
pp. 789-795 ◽  
Author(s):  
George A. Reichard ◽  
A. Gerson Jacobs ◽  
Philip Kimbel ◽  
Norman J. Hochella ◽  
Sidney Weinhouse
Keyword(s):  
Blood Glucose ◽  
Intravenous Injection ◽  
Glucose Utilization ◽  
Specific Activity ◽  
Normal Subjects ◽  
Utilization Rate ◽  
Replacement Rate ◽  
Glucose Levels ◽  
Glucose Carbon ◽  
Blood Glucose Levels

The rate of decrease in specific activity of blood glucose following intravenous injection of uniformly C14–labeled glucose in a series of 13 nondiabetic and 19 diabetic humans was measured over periods of 3—6 hr. In the nondiabetic humans the specific activity decreased exponentially for about 3 hr, then usually slowed down gradually over the next 3 hr. From the curves obtained up to 3 hr, rates of blood glucose replacement were estimated to be 120 mg/kg/hr, with a range of from 84 to 153 mg/kg/hr. The high and fluctuating blood glucose levels of the diabetic subjects made estimations of replacement rate somewhat uncertain, but despite a wider spread of values, the average, at 109 mg/kg/hr, was not markedly different from that of the nondiabetic subjects. Mild diabetics on the whole had a lower replacement rate, whereas severe diabetics had a markedly higher replacement rate than the normal subjects. The proportion of blood glucose carbon appearing in the respiratory CO2 was also similar—in nondiabetics, 25±3%, and in diabetics, 22 ± 5%. Despite the higher glucose pool in the diabetics, the glucose spaces were about the same at 30 ± 5% and 29 ± 3%, respectively. Taking into consideration a glucose utilization rate by brain of 60—70 mg/kg/hr, the turnover data indicate that relatively little of the glucose which enters the blood in the fasting human is used by the peripheral musculature. Submitted on November 25, 1960

scholarly journals Metabolites of 2-Deoxy-[14C]Glucose in Plasma and Brain: Influence on Rate of Glucose Utilization Determined with Deoxyglucose Method in Rat Brain

1993 ◽  
Vol 13 (2) ◽  
pp. 315-327 ◽  
Author(s):  
Gerald A. Dienel ◽  
Nancy F. Cruz ◽  
Louis Sokoloff
Keyword(s):  
Glucose Utilization ◽  
Specific Activity ◽  
Experimental Period ◽  
Postmortem Brain ◽  
Rat Tissues ◽  
Precursor Pool ◽  
Usual Procedure ◽  
Body Tissues ◽  
Metabolite Pool

The [14]deoxyglucose ([14C]DG) method depends upon quantitative trapping of metabolites in brain at the site of phosphorylation, and in the usual procedure it is assumed that all the label in plasma is in free DG. Our previous finding of labeled nonacidic derivatives of DG in plasma raised the possibility that some metabolites of DG might not be fully retained in body tissues and therefore cause overestimation of the integrated specific activity of the precursor pool determined from assay of label in plasma and/or underestimation of the true size of the metabolite fraction in brain. In the present study, metabolism of DG in rat tissues by secondary pathways was examined and found to be more extensive than previously recognized. When 14C-labeled compounds in ethanol extracts of either plasma or brain were separated by anion exchange HPLC, eight fractions were obtained. 14C-labeled metabolites in plasma were detected after a 35-min lag and gradually increased in amount with time after an intravenous pulse. In brain, deoxyglucose-6-phosphate was further metabolized, mainly to deoxyglucose-1-phosphate and deoxyglucose-1,6-phosphate. These are acid-labile compounds and accounted for ∼20% of the 14C in the metabolite pool in brain. The rate constants for net loss of 14C from the metabolite pool between 45 and 180 min after a pulse were similar (0.4–0.5%/min) in vivo and in intact postmortem brain. The rate constant for loss of deoxyglucose-6-phosphate (DG-6-P) in vivo (∼0.7%/min) was, however, about twice that for postmortem brain, suggesting that a significant fraction of the DG-6-P lost in vivo is due to its further metabolism by energy-dependent reactions. 14C-labeled metabolites of [14C]DG in plasma and brain do not interfere with determination of local rates of glucose utilization in brain in normal, conscious rats by the autoradiographic method if the prescribed procedures and a 45-min experimental period are used.

scholarly journals Direct Chemical Measurement of the λ of the Lumped Constant of the [14C]Deoxyglucose Method in Rat Brain: Effects of Arterial Plasma Glucose Level on the Distribution Spaces of [14C]Deoxyglucose and Glucose and on λ

1989 ◽  
Vol 9 (3) ◽  
pp. 304-314 ◽  
Author(s):  
Kentaro Mori ◽  
Nancy Cruz ◽  
Gerald Dienel ◽  
Thomas Nelson ◽  
Louis Sokoloff
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Severe Hypoglycemia ◽  
Plasma Glucose Concentration ◽  
Operational Equation ◽  
Chemical Measurements ◽  
Lumped Constant ◽  
Dg Method ◽  
Arterial Plasma ◽  
Distribution Spaces

The lumped constant in the operational equation of the 2-[14C]deoxyglucose (DG) method contains the factor λ that represents the ratio of the steady-state tissue distribution spaces for [14C]DG and glucose. The lumped constant has been shown to vary with arterial plasma glucose concentration. Predictions based mainly on theoretical grounds have suggested that disproportionate changes in the distribution spaces for [14C]DG and glucose and in the value of λ are responsible for these variations in the lumped constant. The influence of arterial plasma glucose concentration on the distribution spaces for DG and glucose and on λ were, therefore, determined in the present studies by direct chemical measurements. The brain was maintained in steady states of delivery and metabolism of DG and glucose by programmed intravenous infusions of both hexoses designed to produce and maintain constant arterial concentrations. Hexose concentrations were assayed in acid extracts of arterial plasma and freeze-blown brain. Graded hyperglycemia up to 28 m M produced progressive decreases in the distribution spaces of both hexoses from their normoglycemic values (e.g., ∼ – 20% for glucose and – 50% for DG at 28 m M). In contrast, graded hypoglycemia progressively reduced the distribution space for glucose and increased the space for [14C]DG. The values for λ were comparatively stable in normoglycemic and hyperglycemic conditions but rose sharply (e.g., as much as 9–10-fold at 2 m M) in severe hypoglycemia.

Pharmacogenetics of Metformin

2021 ◽  
Vol 1 (6) ◽  
pp. 123-129
Author(s):  
Alrahman Joneri
Keyword(s):  
American Diabetes Association ◽  
Glucose Utilization ◽  
Medical Condition ◽  
World Health ◽  
First Line ◽  
Glucose Levels ◽  
Normal Limits ◽  
The World ◽  
Health Organization ◽  
The Individual

Hyperglycemia is a medical condition in which an increase in glucose levels in the blood exceeds normal limits. Hyperglycemia is one of the typical signs of diabetes mellitus (DM). The World Health Organization (WHO) predicts an increase in the number of people with DM which is a global health threat. Diabetes is the leading cause of kidney failure, and the leading cause of heart disease and stroke, in adults. Metformin, which is a biguanide group, is recommended by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes as the first-line oral therapy for DM and is the most widely used oral medication worldwide. Metformin can also increase peripheral glucose utilization and ultimately decrease the production of fatty acids and triglycerides. Some of the individual differences that underlie the variation in response to metformin.

The appearance and quantitation of cytoplasmic ribonucleic acid in the early chick embryo

Development ◽  
1972 ◽  
Vol 28 (2) ◽  
pp. 367-384
Author(s):  
C. C. Wylie
Keyword(s):  
Chick Embryo ◽  
Ribosomal Rna ◽  
Rna Synthesis ◽  
Specific Activity ◽  
Cell Number ◽  
Present Knowledge ◽  
Precursor Pool ◽  
Cytoplasmic Rna ◽  
Labelling Experiment ◽  
Neurula Stage

This paper seeks to extend our knowledge about RNA synthesis in early embryogenesis to the domestic fowl, Gallus domesticus. Using this species for research, apart from increasing our knowledge of higher vertebrate embryology, has certain advantages such as rapid uptake of isotopic precursors and ease of microdissection in culture. The following results are presented: (1) The cell number in the whole chick embryos is shown to be increasing logarithmically between the time of laying and the early neurula stage; with a doubling time of 7·4 h. (2) The onset of ribosomal RNA synthesis has been shown to be during mid-cleavage of the chick embryo, while development is taking place in the oviduct and uterus of the mother. (3) In a cumulative labelling experiment, embryos were labelled at the unincubated-egg stage, allowed to develop to various morphological stages up to neurulation, and their cytoplasmic RNA prepared and analysed by gel electrophoresis. (4) The specific activity of the precursor pool for RNA synthesis was measured at several stages, using the same labelling conditions, and the results were used to quantitate the RNA synthesis from the incorporated radioactivity. (5) Using these techniques, it was found that newly synthesized cytoplasmic RNA accumulates steadily in the whole chick embryo, reaching a level of 104 μg by the early neurula stage. On a per cell basis, however, the amount of newly synthesized cytoplasmic RNA seems to decrease slightly. These findings are discussed in the light of present knowledge about embryos of other vertebrates and certain invertebrates.

scholarly journals Resistance of Erythrocytes of Hibernating Mammals to Loss of Potassium during Hibernation and during Cold Storage

1971 ◽  
Vol 58 (6) ◽  
pp. 620-633 ◽  
Author(s):  
S. L. Kimzey ◽  
J. S. Willis
Keyword(s):  
Ground Squirrel ◽  
Normal Values ◽  
Ground Squirrels ◽  
Storage Medium ◽  
Cold Adapted ◽  
Maximum Period ◽  
K Concentration

In two species of hibernators, hamsters and ground squirrels, erythrocytes were collected by heart puncture and the K content of the cells of hibernating individuals was compared with that of awake individuals. The K concentration of hamsters did not decline significantly during each bout of hibernation (maximum period of 5 days) but in long-term bouts in ground squirrels (i.e. more than 5 days) the K concentration of cells dropped significantly. When ground squirrels were allowed to rewarm the K content of cells rose toward normal values within a few hours. Erythrocytes of both hamsters and ground squirrels lose K more slowly than those of guinea pigs (nonhibernators) when stored in vitro for up to 10 days at 5°C. In ground squirrels the rate of loss of K during storage is the same as in vivo during hibernation, and stored cells taken from hibernating ground squirrels also lose K at the same rate. The rate of loss of K from guinea pig cells corresponded with that predicted from passive diffusion unopposed by transport. The actual rate of loss of K from ground squirrel cells was slower than such a predicted rate but corresponded with it when glucose was omitted from the storage medium or ouabain was added to it. Despite the slight loss of K that may occur in hibernation, therefore, the cells of hibernators are more cold adapted than those of a nonhibernating mammal, and this adaptation depends in part upon active transport.

scholarly journals LECITHIN SYNTHESIS, INTRACELLULAR TRANSPORT, AND SECRETION IN RAT LIVER

1969 ◽  
Vol 40 (2) ◽  
pp. 461-483 ◽  
Author(s):  
Olga Stein ◽  
Yechezkiel Stein
Keyword(s):  
Endoplasmic Reticulum ◽  
Liver Cell ◽  
Phosphatidyl Choline ◽  
Intracellular Transport ◽  
Phosphatidyl Ethanolamine ◽  
Specific Activity ◽  
Perfused Liver ◽  
Precursor Pool

Injection of choline-3H into choline-deficient rats resulted in an enhanced incorporation of the label into liver lecithin, as compared to the incorporation of label into liver lecithin of normal rats. The results obtained with the use of different lecithin precursors indicate that in the intact liver cell, both in vivo and in vitro, exchange of choline with phosphatidyl-choline is not significant. The synthesis and secretion of lecithins by the choline-deficient liver compare favorably with the liver of choline-supplemented rats, when both are presented with labeled choline or lysolecithin as lecithin precursors. Radioautography of the choline-deficient liver shows that 5 min after injection of choline-3H the newly synthesized lecithin is found in the endoplasmic reticulum (62%), mitochondria (13%), and at the "cell boundary" (20%). The ratio of the specific activity of microsomal and mitochondrial lecithin, labeled with choline, glycerol, or linoleate, was 1.53 at 5 min after injection, but the ratio of the specific activity of phosphatidyl ethanolamine (PE), labeled with ethanolamine, was 5.3. These results indicate that lecithin and PE are synthesized mainly in the endoplasmic reticulum, and are transferred into mitochondria at different rates. The site of a precursor pool of bile lecithin was studied in the intact rat and in the perfused liver. Following labeling with choline-3H, microsomal lecithin isolated from perfused liver had a specific activity lower than that of bile lecithin, but the specific activity of microsomal linoleyl lecithin was comparable to that of bile lecithin between 30 and 90 min of perfusion. It is proposed that the site of the bile lecithin pool is located in the endoplasmic reticulum and that the pool consists mostly of linoleyl lecithin.

Hypoglycemia counterregulation in elderly humans: relationship to glucose levels

1994 ◽  
Vol 267 (4) ◽  
pp. E497-E506 ◽  
Author(s):  
F. J. Ortiz-Alonso ◽  
A. Galecki ◽  
W. H. Herman ◽  
M. J. Smith ◽  
J. A. Jacquez ◽  
...  
Keyword(s):  
Glucose Utilization ◽  
Hepatic Glucose Production ◽  
Severe Hypoglycemia ◽  
Glucose Production ◽  
Counterregulatory Hormones ◽  
Glucose Levels ◽  
Hepatic Glucose ◽  
Consistent Increase ◽  
Step Study ◽  
Elderly Humans

This study was designed to define the effect of human aging on hypoglycemia counterregulatory mechanisms. A hyperinsulinemic (2 mU.kg-1.min-1) glucose clamp procedure was used to control glucose and insulin levels during stepwise lowering of plasma glucose. Counterregulatory hormones, hepatic glucose production (HGP), glucose utilization, and symptoms of hypoglycemia were studied in 13 healthy young [age 24 +/- 1 (SE) yr] and 11 healthy old (age 65 +/- 1 yr) nondiabetic volunteers on two occasions: 1) at matched euglycemia and 70 and 60 mg/dl (study 1) and 2) at matched euglycemia and 60 and 50 mg/dl (study 2). The old had consistently lower epinephrine (P < 0.005), glucagon (P < 0.02), cortisol (P < 0.05), and pancreatic polypeptide (P < 0.02) responses at the 60-mg/dl glucose step in study 1. However, these differences were no longer detectable at the more severe hypoglycemic stimulus of 50 mg/dl in study 2. A consistent increase in HGP occurred in both groups only at the 50-mg/dl glucose step (study 2) and was not different between young and old. There were also no differences in symptom responses between young and old. In summary, we found that elderly individuals have a subtle impairment of the glucose counterregulatory response during moderate hypoglycemia, but this impairment is no longer detectable during more severe hypoglycemia.

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