scholarly journals The fuel of the spleen. Studies using a new method for perfusing the rat spleen with whole blood

1989 ◽  
Vol 263 (2) ◽  
pp. 325-332 ◽  
Author(s):  
M A Mindham ◽  
P A Mayes

1. An improved rat spleen perfusion is described incorporating a method of defibrination which avoids the use of heparin and enables the spleen to be perfused with rat blood for several hours at a haematocrit of 40% and for 12 h or more at a haematocrit of 20%. 2. Glucose oxidation accounted for 11.6% of the total oxygen consumption but this represented only 8% of total glucose uptake, which was largely converted to lactate and released into the perfusate. However, significant amounts of lactate were oxidized. These results can be explained by the presence of at least two cell populations, one emphasizing the anaerobic oxidation of glucose and the other aerobic metabolism, particularly of lactate. 3. Non-esterified fatty acid and 3-hydroxybutyrate, when available at physiological concentrations, were shown to be major oxidative fuels of the spleen. 4. Chylomicron triacylglycerol was hydrolysed readily and taken up, but not oxidized extensively.

2012 ◽  
Vol 303 (7) ◽  
pp. E908-E916 ◽  
Author(s):  
Jiarong Liu ◽  
Wei Zhang ◽  
Gin C. Chuang ◽  
Helliner S. Hill ◽  
Ling Tian ◽  
...  

We have suggested previously that Tribbles homolog 3 (TRIB3), a negative regulator of Akt activity in insulin-sensitive tissues, could mediate glucose-induced insulin resistance in muscle under conditions of chronic hyperglycemia (Liu J, Wu X, Franklin JL, Messina JL, Hill HS, Moellering DR, Walton RG, Martin M, Garvey WT. Am J Physiol Endocrinol Metab 298: E565–E576, 2010). In the current study, we have assessed short-term physiological regulation of TRIB3 in skeletal muscle and adipose tissues by nutrient excess and fasting as well as TRIB3's ability to modulate glucose transport and mitochondrial oxidation. In Sprague-Dawley rats, we found that short-term fasting enhanced insulin sensitivity concomitantly with decrements in TRIB3 mRNA (66%, P < 0.05) and protein (81%, P < 0.05) in muscle and increments in TRIB3 mRNA (96%, P < 0.05) and protein (∼10-fold, P < 0.05) in adipose tissue compared with nonfasted controls. On the other hand, rats fed a Western diet for 7 days became insulin resistant concomitantly with increments in TRIB3 mRNA (155%, P < 0.05) and protein (69%, P = 0.0567) in muscle and a decrease in the mRNA (76%, P < 0.05) and protein (70%, P < 0.05) in adipose. In glucose transport and mitochondria oxidation studies using skeletal muscle cells, we found that stable TRIB3 overexpression impaired insulin-stimulated glucose uptake without affecting basal glucose transport and increased both basal glucose oxidation and the maximal uncoupled oxygen consumption rate. With stable knockdown of TRIB3, basal and insulin-stimulated glucose transport rates were increased, whereas basal glucose oxidation and the maximal uncoupled oxygen consumption rate were decreased. In conclusion, TRIB3 impacts glucose uptake and oxidation oppositely in muscle and fat according to levels of nutrient availability. The above data for the first time implicate TRIB3 as a potent physiological regulator of insulin sensitivity and mitochondrial glucose oxidation under conditions of nutrient deprivation and excess.


1960 ◽  
Vol 198 (4) ◽  
pp. 807-810 ◽  
Author(s):  
Irving B. Fritz

The metabolic fate of glucose in isolated muscle after addition of insulin was shown to be dependent upon the functional state of the tissue. While nonstimulated muscle responded primarily with an increased incorporation of glucose into glycogen, stimulated muscle showed predominantly an increased conversion of labeled glucose to CO2 following insulin addition. The oxidation of palmitic-1-C14 acid by muscle was not influenced by the presence of insulin. Ryanodine, used as a chemical agent for inducing contraction of diaphragm, resulted in stimulation of oxygen consumption, fatty acid oxidation and glucose oxidation to an extent comparable to that previously achieved with electrical stimulation of muscle. The conclusion was reached that insulin increased the oxidation of glucose but not of palmitate, and that the specific metabolic fate of intracellular glucose is not influenced by insulin. The data are discussed in relation to the prevailing theory that insulin acts by increasing permeability of muscle cell membranes to certain substrates.


1965 ◽  
Vol 43 (4) ◽  
pp. 437-450 ◽  
Author(s):  
A. S. W. de Freitas ◽  
Florent Depocas

The extent of incorporation of glucose carbon into total lipids and component fatty acid, neutral glyceride glycerol, and phosphoglyceride glycerol moieties of carcass, liver, and epididymal tissue has been measured in 20 rats under conditions of constant plasma glucose concentration and specific activity. Rates of fatty acid synthesis from glucose and absolute rates of synthesis have also been estimated. Each rat received 750 mg glucose per hour by continuous infusion. The incorporation of glucose carbon into carcass, liver, and epididymal fat was, respectively, 6.2, 0.75, and 0.06% of the total glucose carbon taken up by the rat tissues. Fifty percent of the C14 found in total lipids of carcass and liver was in the fatty acid fraction. Corresponding glyceride glycerol moieties contained approximately 40% of the total activity. The low level of incorporation of glucose carbon into fatty acids and glyceride glycerol indicates that lipogenesis from glucose can only account for a small proportion of the total glucose taken up by the tissues, even at high rates of glucose uptake. Rates of synthesis from glucose of carcass and liver fatty acids were estimated as 1.5 and 0.11 mmoles fatty acid per tissue per day respectively, with corresponding half-lives of 57 and 7.6 days. Absolute rates of fatty acid synthesis were estimated as 2.6 and 0.55 mmoles fatty acid per day for carcass and liver tissue respectively, with corresponding half-lives of 34 and 4.6 days.


2001 ◽  
Vol 281 (2) ◽  
pp. E335-E340 ◽  
Author(s):  
Virendar K. Kaushik ◽  
Martin E. Young ◽  
David J. Dean ◽  
Theodore G. Kurowski ◽  
Asish K. Saha ◽  
...  

Previous studies have shown that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a cell-permeable activator of AMP-activated protein kinase, increases the rate of fatty acid oxidation in skeletal muscle of fed rats. The present study investigated the mechanism by which this occurs and, in particular, whether changes in the activity of malonyl-CoA decarboxylase (MCD) and the β-isoform of acetyl-CoA carboxylase (ACCβ) are involved. In addition, the relationship between changes in fatty acid oxidation induced by AICAR and its effects on glucose uptake and metabolism was examined. In incubated soleus muscles isolated from fed rats, AICAR (2 mM) increased fatty acid oxidation (90%) and decreased ACCβ activity (40%) and malonyl-CoA concentration (50%); however, MCD activity was not significantly altered. In soleus muscles from overnight-fasted rats, AICAR decreased ACCβ activity (40%), as it did in fed rats; however, it had no effect on the already high rate of fatty acid oxidation or the low malonyl-CoA concentration. In keeping with its effect on fatty acid oxidation, AICAR decreased glucose oxidation by 44% in fed rats but did not decrease glucose oxidation in fasted rats. It had no effect on glucose oxidation when fatty acid oxidation was inhibited by 2-bromopalmitate. Surprisingly, AICAR did not significantly increase glucose uptake or assayable AMP-activated protein kinase activity in incubated soleus muscles from fed or fasted rats. These results indicate that, in incubated rat soleus muscle, 1) AICAR does not activate MCD or stimulate glucose uptake as it does in extensor digitorum longus and epitrochlearis muscles, 2) the ability of AICAR to increase fatty acid oxidation and diminish glucose oxidation and malonyl-CoA concentration is dependent on the nutritional status of the rat, and 3) the ability of AICAR to diminish assayable ACC activity is independent of nutritional state.


2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Kedryn K Baskin ◽  
Chad E Grueter ◽  
Christine M Kusminski ◽  
Philipp E Scherer ◽  
Rhonda Bassel-Duby ◽  
...  

Background: The heart is a metabolic organ that primarily utilizes fatty acids as energy substrate. While it is well established that the heart is metabolically flexible, the transcriptional network regulating cardiac metabolism is only partially understood. We have previously demonstrated that cardiac overexpression of Med13, a component of the Mediator Complex that regulates transcription, results in a lean phenotype with enhanced basal metabolic rates. We now investigate the mechanisms contributing to metabolic changes in mice with cardiac over-expression of Med13(Med13cTg). Methods and Results: Cardiac fludeoxyglucose (18F-FDG)-PET imaging analysis revealed that Med13cTg hearts take up more glucose than wild type littermates. To determine pathways responsible for enhanced glucose uptake, ventricles from Med13cTg mice were subjected to RNA-seq and metabolomic analysis. The expression of fatty acid oxidation genes was decreased in Med13cTg hearts, accompanied by an increase in acyl CoA and a decrease in acetyl CoA. These data suggest that beta oxidation is decreased in Med13cTg hearts. Mitochondria function was therefore determined in Med13cTg hearts by performing electron-flow analyses and assessing oxygen consumption rates. Indeed, oxygen consumption rates were decreased in mitochondria isolated from Med13cTg hearts. Expression of Krebs Cycle genes and corresponding intermediary metabolites were also decreased in Med13cTg hearts, suggesting decreased flux through this pathway as well. Conclusions: Overexpression of Med13 in the heart increases glucose uptake and decreases fatty acid oxidation in the heart. We speculate that Med13 transcriptionally regulates key mediators of cardiac metabolism. The mechanisms by which this occurs are currently under investigation.


Blood ◽  
1950 ◽  
Vol 5 (12) ◽  
pp. 1114-1124 ◽  
Author(s):  
RICHARD DAY ◽  
ELISE PERRY

Abstract Severe degrees of intravascular red cell agglutination have been observed during life in rats injected with anti-rat red cell serum and in a patient of 11 months with chronic acquired hemolytic anemia. There was no significant fall in the tissue oxygen tension or in the total oxygen consumption of the rats. Neither the rats nor the infant developed kernicterus. In a baby dying with kernicterus no true hemagglutination was observed, although there was slight sludging such as is seen in many illnesses. Additional support for the belief that the red cells in this case were not clumped lies in the fact that in vitro clumping was not observed; furthermore, the sedimentation rate was only 1 mm. in one hour. The blood of the injected rats and of the other infant who did not develop kernicterus sedimented extremely rapidly and displayed spontaneous agglutination in vitro. These observations indicate that intravascular agglutination has little if any bearing on the development of kernicterus in erythroblastosis fetalis.


2001 ◽  
Vol 355 (2) ◽  
pp. 389-395 ◽  
Author(s):  
Wolfgang WIESER ◽  
Gerhard KRUMSCHNABEL

The original aim of the present study was to deal with two problems that had emerged from a study on hierarchies of ATP-consuming processes in cells [Buttgereit and Brand (1995) Biochem. J. 312, 163-167]. Firstly, we wanted to find out whether the results of that study had been influenced by the method used for the determination of process activity and, secondly, we wondered whether and to what extent the structure of the hierarchy established for cell suspensions under energy-limiting conditions might depend on the type of cell or on the lifestyle, ecology and phylogenetic status of the species from which the cells were derived. We confined our study to the two most prominent ATP consumers of cells: protein synthesis and the Na+/K+-ATPase, measuring their activity directly by [3H]leucine incorporation and Rb+-flux respectively. We found large differences in the sensitivity of protein synthesis to energy limitation between hepatocytes from an anoxia-tolerant fish species and an anoxia-sensitive fish species (goldfish and rainbow trout respectively). On the other hand, Na+/K+-ATPase activity was hardly affected by energy limitation in the hepatocytes from both fish species. We also studied the response of a human hepatoma cell line, HepG2, to energy limitation and found both protein synthesis and Na+/K+-ATPase activity to be equally sensitive to energy limitation, but more sensitive than the Na+/K+-ATPase of the two fish species. A comparison of the indirect and direct methods for measuring protein synthesis revealed the rate of oxygen consumption to be functionally related to the concentration of cycloheximide, the inhibitor used. It was found that at 15mM cycloheximide [three orders of magnitude higher than the concentration at which the incorporation of free amino acids (FAA) into protein is inhibited] total oxygen consumption was suppressed by 71-75%, whereas the measured rate of [3H]leucine incorporation into protein suggested that the cycloheximide-sensitive fraction should have amounted to not more than approx. 10% of the total oxygen consumption. On the other hand, the amount of oxygen consumption suppressed with the high concentration of cycloheximide corresponded almost exactly to the increase in oxygen consumption of cells incubated in an FAA-enriched medium compared with cells incubated in a standard, FAA-free medium. Our major conclusions are, firstly, that high concentrations of cycloheximide disrupt cellular metabolism, bringing to a standstill all those processes that can be stimulated by incubating starved cells in an FAA-enriched medium, secondly, that the attempt to estimate the metabolic cost of protein synthesis by inhibiting oxygen consumption with cycloheximide leads to spurious results, and, thirdly, that the structure of a ‘hierarchy’ of ATP-consumers may reflect the lifestyle and physiology of the species studied.


Diabetes ◽  
1982 ◽  
Vol 31 (11) ◽  
pp. 957-963 ◽  
Author(s):  
D. Thiebaud ◽  
E. Jacot ◽  
R. A. Defronzo ◽  
E. Maeder ◽  
E. Jequier ◽  
...  

1964 ◽  
Vol 206 (1) ◽  
pp. 119-123 ◽  
Author(s):  
Florent Depocas

Rates of turnover, excretion, and oxidation of glucose have been measured in alloxan-diabetic rats and compared to values obtained in normal rats under similar conditions. Alloxan-diabetic rats showed almost normal rates of glucose uptake (turnover rate-excretion rate) but at levels of plasma glucose approximately 3.4 times normal. Under these conditions the ratio of oxidation rate to uptake rate of glucose in alloxan-diabetic rats was very close to that measured in normal animals, thus indicating that lowered availability of insulin does not modify the pattern of intracellular regulation of glucose oxidation which in the normal animal is a function of the rate of glucose uptake by the tissues.


1987 ◽  
Vol 245 (3) ◽  
pp. 789-793 ◽  
Author(s):  
D Isler ◽  
H P Hill ◽  
M K Meier

To quantify the potential of brown adipose tissue as a target organ for glucose oxidation, O2 consumption and glucose metabolism in isolated rat brown adipocytes were measured in the presence and absence of insulin, by using the beta-agonists isoprenaline or Ro 16-8714 to stimulate thermogenesis. Basal metabolic rate (278 mumol of O2/h per g of lipid) was maximally stimulated with isoprenaline (20 nm) and Ro 16-8714 (20 microM) to 1633 and 1024 mumol of O2/h per g respectively, whereas insulin had no effect on O2 consumption. Total glucose uptake, derived from the sum of [U-14C]glucose incorporation into CO2 and total lipids and lactate release, was enhanced with insulin. Isoprenaline and Ro 16-8714 had no effect on insulin-induced glucose uptake, but promoted glucose oxidation while inhibiting insulin-dependent lipogenesis and lactate production. A maximal value for glucose oxidation was obtained under the combined action of Ro 16-8714 and insulin, which corresponded to an equivalent of 165 mumol of O2/h per g of lipid. This makes it clear that glucose is a minor substrate for isolated brown adipocytes, fuelling thermogenesis by a maximum of 16%.


Sign in / Sign up

Export Citation Format

Share Document