ISSN:0148-6071    

DOI:10.1177/014860719101500328

出版商:SAGE Publications    

年代:1991

数据来源: WILEY

摘要:

Quantitative assessment of substrate metabolism fromin vivotracer kinetic data requires a model of the system, i.e., a hypothesis on the structure and functioning of the system. Some fundamentals of modeling important for studying intermediary metabolism in the steady state will be discussed. Accessible pool and system parameters are defined. Although the calculation of accessible pool parameters is structure‐free, that of system parameters requires the use of noncompartmental or compartmental structures. Assumptions, bases for choice, and relative merits of these two modeling strategies are discussed. Glucose and leucine metabolism serve as prototypes to illustrate the theoretical points. (Journal of Parenteral and Enteral Nutrition15:45S‐50S, 1991)

ISSN:0148-6071    

DOI:10.1177/014860719101500345S

出版商:SAGE Publications    

年代:1991

数据来源: WILEY

摘要:

The metabolism of amino acids is far more complicated than a 1‐ to 2‐pool model. Yet, these simple models have been extensively used with many different isotopically labeled tracers to study protein metabolism. A tracer of leucine and measurement of leucine kinetics has been a favorite choice for following protein metabolism. However, administering a leucine tracer and following it in blood will not adequately reflect the complex multi‐pool nature of the leucine system. Using the tracer enrichment of the ketoacid metabolite of leucine, a‐ketoisocaproate (KIC), to reflect intracellular events of leucine was an important improvement. Whether this approach is adequate to follow accurately leucine metabolismin vivoor not has not been tested. From data obtained using simultaneous administration of leucine and KIC tracers, we developed a 10‐pool model of thein vivoleucine‐KIC and bicarbonate kinetic system. Data from this model were compared with conventional measurements of leucine kinetics. The results from the 10‐pool model agreed best with the simplified approach using a leucine tracer and measurement of KIC enrichment. (Journal of Parenteral and Enteral Nutrition15:505–545, 1991)

ISSN:0148-6071    

DOI:10.1177/014860719101500350S

出版商:SAGE Publications    

年代:1991

数据来源: WILEY

摘要:

In experiments on biological systems one often cannot measure all state variables (compartments). Given a particular experiment of that type, a basic kinetic parameter may have no effect on the observations; such a parameter is an insensible parameter for that experiment. A parameter may influence the observations and not be uniquely determinable; such a parameter is nonidentifiable for that experiment. Only identifiable parameters can be estimated uniquely, by that experiment. I review the basic theory to check identifiability for a nominal value of a parameter (local identifiability), and present some examples of problems that may arise in estimation. (Journal of Parenteral and Enteral Nutrition15:55S‐59S, 1991)

ISSN:0148-6071    

DOI:10.1177/014860719101500355S

出版商:SAGE Publications    

年代:1991

数据来源: WILEY

摘要:

A new type of model called adepartmentis formulated to complement the compartment. While a compartment may be dominated by convective transport, a department is dominated by diffusive transport. Although exit from a compartment is limited by the rate of biophysical or biochemical removal (“kC”), exit from a department is limited by the rate of transport to the site of biophysical or biochemical removal. (Journal of Parenteral and Enteral Nutrition15:59S‐64S, 1991)

ISSN:0148-6071    

DOI:10.1177/014860719101500359S

出版商:SAGE Publications    

年代:1991

数据来源: WILEY

摘要:

The ideal tracer for metabolic studies is one that behaves exactly like the tracee. Compounds labeled with isotopes come the closest to this ideal because they are chemically identical to the tracee except for the substitution of a stable or radioisotope at one or more positions. Even this substitution, however, can introduce a difference in metabolism that may be quantitatively important with regard to the development of the mathematical model used to interpret the kinetic data. The doubly labeled water method for the measurement of carbon dioxide production and hence energy expenditure in free‐living subjects is a good example of how differences between the metabolism of the tracers and the tracee can influence the accuracy of the carbon dioxide production rate determined from the kinetic data. (Journal of Parenteral and Enteral Nutrition15:64S‐67S, 1991)

ISSN:0148-6071    

DOI:10.1177/014860719101500364S

出版商:SAGE Publications    

年代:1991

数据来源: WILEY

摘要:

Most publications on modeling present only the final product without describing the details as to how they were developed and tested. It is, however, by model development and testing that the true power of modeling as a research tool reveals itself. The purpose of this paper is to present a “behind the scenes” look at a set of experiments designed to study carbon atom transport in gluconeogenesis. In particular, it will be shown how the development of one model led to hypotheses for which another set of experiments was designed. The model which resulted from the second study contained in turn a number of new hypotheses for which further experiments remain to be designed. The second model supported the findings of the first, and yielded deeper insights into the exchange of carbon atoms among three metabolites. It is hoped this illustration will encourage other investigators to take advantage of the utilitarian value of modeling not only as a parameter generating tool, but also as a true research tool which can aid significantly to extract more information from available data. (Journal of Parenteral and Enteral Nutrition15:67S‐71S, 1991)

ISSN:0148-6071    

DOI:10.1177/014860719101500367S

出版商:SAGE Publications    

年代:1991

数据来源: WILEY

摘要:

The regulation of net hepatic glucose uptakein vivooccurs by way of the hormonal milieu (insulin and glucagon), the glucose level, and the route of glucose delivery. Hyperglycemia in the absence of changes in pancreatic hormones (i.e., increased insulin and/or decreased glucagon) does not elicit significant glucose uptake by the liver. Net hepatic glucose uptake is augmented in a dose‐dependent manner by a rise in insulin and is further stimulated by the presence of a “portal signal.” The presence of coordinated changes in insulin, glucagon, and the glucose level in combination with the “portal signal” ensures adequate glucose uptake by the liver in response to a meal. (Journal of Parenteral and Enteral Nutrition15:71S‐73S,1991)

ISSN:0148-6071    

DOI:10.1177/014860719101500371S

出版商:SAGE Publications    

年代:1991

数据来源: WILEY

摘要:

Compounds that can be given safely in large quantity, conjugate with intermediates of carbohydrate metabolism in liver, and are then excreted, allow large amounts of those intermediates to be isolated noninvasively. By administering labeled compounds that form those intermediates and determining the amount and/or distribution of label in those intermediates, the metabolism of those compounds can be traced. Thus, glucuronide formation has been used to sample hepatic uridine diphosphate glucose (UDP‐glucose) and study glycogen metabolism and the pentose pathway, phenylacetate to sample hepatic α‐ketoglutarate and estimate relative flux through the Krebs cycle, and acetylation to sample hepatic acetyl CoA. Interpretations require knowledge of the anatomical sites of formation of the intermediates, since more than one pool of an intermediate can exist in liver. The extent the labeled compound is metabolized in extrahepatic tissues also must be taken into account. (Journal of Parenteral and Enteral Nutrition15:74S‐77S, 1991)

ISSN:0148-6071    

DOI:10.1177/014860719101500374S

出版商:SAGE Publications    

年代:1991

数据来源: WILEY

摘要:

It was shown that the liver is not the major site of removal of glucose after a carbohydrate meal in man. Fractional extractions varied from 5 to 10%. Alternative substrates for postprandial hepatic glycogen synthesis were therefore sought. It was demonstrated that, in man, about 60% of hepatic glycogen was formed from gluconeogenetic substrates. Since significant excursions occur only in plasma lactate after glucose loading, this was deemed the most likely substrate under these circumstances. By differential sampling across the liver and the gut in a conscious pig model, it was found that the liver takes up enough lactate (fractional extraction of 40–50%) to account for the gluconeogenetic production of glycogen. Forty percent of this arises from the gut. Muscle (as represented by the forearm in man) does not contribute lactate during glucose loading, suggesting that other tissues such as the skin are of importance. The gluconeogenetic process may be an important site for the obligatory tissue production of lactate. (Journal of Parenteral and Enteral Nutrition15:77S‐81S, 1991)

ISSN:0148-6071    

DOI:10.1177/014860719101500377S

出版商:SAGE Publications    

年代:1991

数据来源: WILEY