Interrelationship and control of glucose metabolism and lipogenesis in isolated fat-cells. Control of pentose phosphate-cycle activity by cellular requirement for reduced nicotinamide adenine dinucleotide phosphate

Kather, H; Rivera, Madison E.; Brand, Karl

doi:10.1042/bj1281097

Cited by 49 publications

(14 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Quantitative agreement with literature data was also found for the calculated fluxes of several pathways whose intermediates were not directly measured in this study. For example, our model indicated that the PPP supplies 60% of the NADPH needed for fatty acid synthesis in mature adipocytes, which is in excellent agreement with the results of isotopic tracer studies (14,22,24). A current estimate (46) for the oxygen uptake rate of day 14 postinduction 3T3-L1 cells is 2.9 nmol/min per 4ϫ10 5 cells, or 1,147 mmol⅐g DNA Ϫ1 ⅐2 days Ϫ1 (assuming a conversion factor of 18.2 pg DNA/cell; unpublished observation), which is quantitatively similar to the rates calculated in this study (626 and 801 mmol⅐g DNA Ϫ1 ⅐2 days Ϫ1 , respectively, for TCP and collagen cultures at day 16).…”

Section: Discussionsupporting

confidence: 85%

“…Third, biochemistry textbooks (27,42) and the published literature (12) were consulted to eliminate enzymes thought to be inactive in the fed state. Finally, the following assumptions were applied: 1) glycogen synthesis is negligible (22); 2) fatty acid oxidation is small compared with both lipogenesis and lipolysis (47); 3) the pentose phosphate pathway (PPP) is operating in the oxidative mode (6); and 4) net protein synthesis is small compared with metabolic fluxes (17). The stoichiometric model was rendered into a compound, directed graph, visualized using the Bioinformatics toolbox of MATLAB (MathWorks, Natick, MA), and corrected for missing steps and nonsensical dead ends.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Flux profile and modularity analysis of time-dependent metabolic changes of de novo adipocyte formation

Yoon²,

Lee³

2007

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

White adipose tissue (WAT) mass is the main determinant of obesity and associated health risks. WAT expansion results from increases in white adipocyte cell number and size, which in turn reflect a series of shifts in the cellular metabolic state. To quantitatively profile the metabolic alterations occurring during de novo adipocyte formation, metabolic flux analysis (MFA) was used in conjunction with a novel modularity analysis algorithm on differentiating 3T3-L1 preadipocytes. Use of a type I collagen gel as an effective long-term culture substrate was also assessed. The calculated flux distributions predicted the sequential activation of several intracellular cross-compartmental pathways, including lipogenesis, the pentose phosphate pathway, and the malate cycle, in good agreement with earlier isotopic tracer experiments and gene profiling studies. Partition of the adipocyte metabolic network into highly interacting reaction subgroups suggested a functional reorganization of the major pathways consistent with the lipid-loading phenotype of the adipocyte. Flux and modularity analysis results together point to the flux distribution around pyruvate as a key indicator of adipocyte lipid accumulation.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Methodsmentioning

confidence: 99%

Flux profile and modularity analysis of time-dependent metabolic changes of de novo adipocyte formation

Yoon²,

Lee³

2007

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…Conversion of glucose-6-phosphate to pyruvate is blocked by fluoride (21), and the rate of the pentose phosphate pathway is augmented by the addition of PMS, an agent which permits rapid oxidation of NADPH to NADP. In cells treated in this manner, the regulation of the pentose phosphate pathway by the NADP/NADPH ratio is bypassed (22)(23)(24)(25). In such a system, the conversion of [ Insulin, where present, was at a concentration of 500 microunits/ml.…”

mentioning

confidence: 99%

Effect of 3':5'-cyclic AMP on glucose transport in rat adipocytes.

Taylor¹,

Mak²,

Halperin³

1976

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

An indirect method for obtaining a reliable measure of the rate of glucose transport into adipocytes is described. Evidence is presented that altered levels of 3':5'-cyclic AMP can influence the transport of glucose into adipocytes. When cyclic AMP levels were lowered with antilipolytic agents (insulin, nicotinic acid, or clofibrate), rates of glucose transport were increased. In contrast, when adipose tissue levels of cyclic AMP were elevated by lipolytic hormones or theophylline, glucose transport was inhibited. Insulin no longer increased glucose transport when cyclic AMP levels were elevated by lipolytic agents. Agents that can raise cyclic AMP but inhibit lipolysis (procaine, amitryptyline, and phenylethylbiguanide) reduced the rate of glucose transport. Other data are presented that are consistent with the conclusion that cyclic AMP inhibits glucose transport into adipocytes.The relatively small intracellular water volume in adipose tissue makes it technically difficult to measure rates of glucose transport into adipocytes (1). This rate is usually determined by measuring the volume of distribution of added glucose or derivatives in cells rapidly separated from the incubation medium or by measuring countertransport from prelabeled adipocytes (1-9). However, these methods suffer from the disadvantage that incubation is required at reduced temperature or for very short time intervals. The magnitude of the response of the glucose transport system in adipocytes to insulin as observable by previously used methods is small compared to the observed increases in rates of glucose metabolism. Consequently, a considerable portion of information relating to glucose transport in adipose tissue has been inferred from indirect techniques in which glucose utilization has been measured (10-12). Even though these indirect techniques do not clearly dissociate effects on glucose transport from effects on subsequent glucose metabolism, it is generally accepted that insulin stimulates glucose transport in adipose tissue (for review, see ref. 13).Addition of insulin to adipose tissue results in a fall in levels of 3':5'-cyclic AMP (cAMP) (for review, see refs. 13 and 14). Evidence is lacking, however, that the insulin-induced decrease in cAMP is directly associated with increased glucose transport. The apparent absence of an influence of cAMP on glucose transport is incompatible with the possibility of a unitary concept that would link the major metabolic effects of insulin to its actions on intracellular cAMP levels (15).In this report, we first describe a method to determine the rate of glucose transport in adipocytes. This technique offers several advantages over those previously described in that incubation is permitted at normal temperatures for longer periods. Using this method, we then report observations demonstrating an inverse correlation between adipocyte cAMP levels and the rate of glucose transport. On the basis of these data, we discuss the hypothesis that the major actions of insulin in adipose tissue may ...

show abstract

“…Greenbaum, Gumaa and McLean (13) have suggested that conitrol of the pentlose phosphate cycle might well be through a shift in the ratio of NAD+ to NADH. This concept of mass action control has also been suggested from studies on fat cells ( 14), and on erythrocytes (1 5 ) .…”

mentioning

confidence: 90%

Nicotinamide Adenine Dinucleotide (NAD) Content of Liver with Hemorrhagic Shock

Wurth

Sayeed

Baue

1973

Experimental Biology and Medicine

View full text Add to dashboard Cite

An earlier report by Loiselle and Denstedt ( I ) has shown a progressive conversion of the pyridine nucleotides to the reduced form in the livers of rats during shock. This shift was more pronounced in mitochondria than in the cytoplasmic fraction. Work from our laboratory has shown that nicotinamide adenine dinucleotide (NAD) -linked substrates for oxidative phosphorylation are the more sensitive substrates for detecting changes in the functional capability of mitochondria of livers of rats in hemorrhagic shock (2). These studies suggest alteration in the pyridine mcleotide redox state and/ or mitochondria1 contents in shock. In addition to the mitochondria1 enzymes which require NAD as a cofactor for cellular respiration, there are numerous cytoplasmic enzymes which require NAD (3). The nicotinamide adenine dinucleotides are also involved in fatty acid and steroid metabolism and in the excretory functions which involve conjugation (4, 5). Thus the amount as well as the redox state of nicotinamide adenine dinucleotides might be extremely important to cellular function. It semed desirable, therefore, to determine whether the levels of these compounds in the liver of animals were altered by hemorrhagic shock and, if changes took place, could they be reversed by restoring the blood and fluid volume of the animal.Methods. Male, albino rats of the Holtzman strain weighing 200-300 g were used. All animals were fasted 18 to 20 hr and operated in the morning. The animals were given ether anesthesia and both femoral arteries 1Th.k work was supported by grants from the US. Public Health Service No. 5 R01 HL 12278-05 and US. Army Contract No. DADA 17-69-C-9165.were cannulated, one for bleeding into a glass syringe reservoir and the other for measurement of arterial blood pressure. They were restrained in a supine position. After the animals had awakened, hemorrhagic shock was produced by bleeding to a mean arterial pressure of 40 mm Hg which was maintained by withdrawing or giving blood. Details of bhe procedure have been reported previously Six categories of animals were studied: (a) Unbled controls: Nine animals were anesthetized, cannulated and allowed to awaken, but were not bled. They were killed 1 hr after recovery from anesthesia. (b) Shock, Stage I: Eight animals were bled to a mean arterial pressure of 40 mm Hg and maintained until the pressure stabilized with no further withdrawal of blood and sacrificed at that time (about 0.5 hr). (c) Shock, Stage 11: Eight animals were bled, maintained a t a mean arterial pressure of 40 mm Hg and sacrificed when 25% of the shed blood was given back to the animal to maintain the hypotension (about 1 hr). (d) Stage II-Treated: Eight animals were bled and maintained at 40 mm Hg arterial pressure as above. When 25% of the shed blood was given back, the animals were treated by giving the remaining shed blood plus Ringer's lactate solution with 5% dextrose in a volume equal to 50% of the maximum volume of the shed blood. These animals were sacrificed 1 hr after the treatment. (e) Sh...

show abstract

Interrelationship and control of glucose metabolism and lipogenesis in isolated fat-cells. Control of pentose phosphate-cycle activity by cellular requirement for reduced nicotinamide adenine dinucleotide phosphate

Cited by 49 publications

References 16 publications

Flux profile and modularity analysis of time-dependent metabolic changes of de novo adipocyte formation

Flux profile and modularity analysis of time-dependent metabolic changes of de novo adipocyte formation

Effect of 3':5'-cyclic AMP on glucose transport in rat adipocytes.

Nicotinamide Adenine Dinucleotide (NAD) Content of Liver with Hemorrhagic Shock

Contact Info

Product

Resources

About