1,721,014 research outputs found
Minimal model of glucose/insulin dynamics in the intact organism. A novel approach for evaluation of factors controlling glucose tolerance.
One of the major goals in metabolic physiology is the development of methods to quantify specific processes involved in carbohydrate metabolism regulation in the intact organism. In this paper we propose a novel non-invasive (as compared to other techniques) approach for estimating in vivo glucose-insulin dynamic interactions. The rationale of the approach lies in the interpretation of glucose/insulin dynamic data, obtained after a system perturbation, with two mathematical models: particular attention is devoted to the selection of these two models. A minimal, or parsimonious, modelling strategy is proposed, that is, the two models are selected out of two series of physiologically based models, respectively; six of glucose disappearance; and six of insulin secretion and kinetics, according to a set of specific criteria. The two chosen minimal models of glucose metabolism and insulin secretion permit a quantitative insight into the metabolic state of an intact organism by providing accurate estimates of parameters such as insulin sensitivity and pancreatic sensitivity to glucose. Possible physiological and clinical uses of the two models for in vivo quantitative studies of glucose/insulin interactions are discussed, together with the insight that these models seem to provide into the intimate nature of metabolic contro
Physiologic evaluation of factors controlling glucose tolerance in man. Measurement of insulin sensitivity and B-cell glucose sensitivity from the response to intravenous glucose.
The quantitative contributions of pancreatic responsiveness and insulin sensitivity to glucose tolerance were measured using the "minimal modeling technique" in 18 lean and obese subjects (88-206% ideal body wt). The individual contributions of insulin secretion and action were measured by interpreting the dynamics of plasma glucose and insulin during the intravenous glucose tolerance test in terms of two mathematical models. One, the insulin kinetics model, yields parameters of first-phase (phi 1) and second-phase (phi 2) responsivity of the beta-cells to glucose. The other glucose kinetics model yields the insulin sensitivity parameters, SI. Lean and obese subjects were subdivided into good (KG greater than 1.5) and lower (KG less than 1.5) glucose tolerance groups. The etiology of lower glucose tolerance was entirely different in lean and obese subjects. Lean, lower tolerance was related to pancreatic insufficiency (phi 2 77% lower than in good tolerance controls [P less than 0.03]), but insulin sensitivity was normal (P greater than 0.5). In contrast, obese lower tolerance was entirely due to insulin resistance (SI diminished 60% [P less than 0.01]); pancreatic responsiveness was not different from lean, good tolerance controls (phi 1: P greater than 0.06; phi 2: P greater than 0.40). Subjects (regardless of weight) could be segregated into good and lower tolerance by the product of second-phase beta-cell responsivity and insulin sensitivity (phi 2 . SI). Thus, these two factors were primarily responsible for overall determination of glucose tolerance. The effect of phi 1 was to modulate the KG value within those groups whose overall tolerance was determined by phi 2 . SI. This phi 1 modulating influence was more pronounced among insulin sensitive (phi 1 vs. KG, r = 0.79) than insulin resistant (obese, low tolerance; phi 1 vs. KG, r = 0.91) subjects. This study demonstrates the feasibility of the minimal model technique to determine the etiology of impaired glucose tolerance
Quantitative estimation of Beta-cell sensitivity to glucose in the intact organism.
We propose an approach to quantifying the sensitivity of B cells to glucose in the intact organism, whereby we interpret the complex dynamic plasma insulin response to glucose injection in terms of a minimal mathematical model of posthepatic insulin delivery and insulin clearance. The best model for this purpose was chosen by comparing the ability of a series of proposed models to account precisely for plasma insulin dynamics. Intravenous glucose tolerance tests (IVGTT) (300 mg/kg) were performed on conscious dogs, and blood was sampled frequently until the basal steady state was reestablished. Glucose injection produced variable plasma insulin responses, which were characterized by an early peak (76 microU/ml above basal), a plateau with occasional additional peaks, and by an abrupt return of plasma insulin to basal by 37 min. A set of eight models was examined; one emerged as superior, in that it was able to account for insulin dynamics with the smallest number of physiologically meaningful parameters (N = 4). The chosen (minimal) model assumes that (1) clearance of insulin is of the first order, (2) the initial peak represents a bolus of insulin loaded into the plasma after the glucose injection, and (3) the rate of the secondary rise in insulin is determined by the concentration of glucose in plasma above a specific threshold value. The sensitivity of first phase insulin delivery to glucose (phi 1; 1.28 +/- 0.15 microU/ml per min per mg/dl), the sensitivity of the secondary phase to glucose concentration [phi 2; 0.038 +/- 0.005 (microU/mg) . min-2], and the threshold for glucose stimulation of second phase secretion (h; 125 +/- 8 mg/100 ml) were all precisely estimated from the dynamic insulin responses. These three parameters of insulin kinetics (phi 1, phi 2, and h) can be calculated from a single IVGTT, and they characterize the insulin responsiveness of a single individual. Estimating these characteristic parameters of insulin kinetics from IVGTT data has potential for quantitating the individual factors contributing to glucose-stimulated insulin secretion in intact animal models, and it may be applicable to man
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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