scholarly journals Paracrine regulation of glucagon secretion: the β/α/δ model

2016 ◽  
Vol 310 (8) ◽  
pp. E597-E611 ◽  
Author(s):  
Margaret Watts ◽  
Joon Ha ◽  
Ofer Kimchi ◽  
Arthur Sherman
Keyword(s):  
Mathematical Model ◽  
Potassium Channels ◽  
Mathematical Models ◽  
Glucagon Secretion ◽  
Inhibitory Effect ◽  
Β Cells ◽  
Paracrine Regulation ◽  
Intrinsic Mechanism ◽  
Effect Of Glucose ◽  
Do So

The regulation of glucagon secretion in the pancreatic α-cell is not well understood. It has been proposed that glucose suppresses glucagon secretion either directly through an intrinsic mechanism within the α-cell or indirectly through an extrinsic mechanism. Previously, we described a mathematical model for isolated pancreatic α-cells and used it to investigate possible intrinsic mechanisms of regulating glucagon secretion. We demonstrated that glucose can suppress glucagon secretion through both ATP-dependent potassium channels (KATP) and a store-operated current (SOC). We have now developed an islet model that combines previously published mathematical models of α- and β-cells with a new model of δ-cells and use it to explore the effects of insulin and somatostatin on glucagon secretion. We show that the model can reproduce experimental observations that the inhibitory effect of glucose remains even when paracrine modulators are no longer acting on the α-cell. We demonstrate how paracrine interactions can either synchronize α- and δ-cells to produce pulsatile oscillations in glucagon and somatostatin secretion or fail to do so. The model can also account for the paradoxical observation that glucagon can be out of phase with insulin, whereas α-cell calcium is in phase with insulin. We conclude that both paracrine interactions and the α-cell's intrinsic mechanisms are needed to explain the response of glucagon secretion to glucose.

scholarly journals A new mathematical model of phyllotaxis to solve the genuine puzzle spiromonostichy

2021 ◽  
Author(s):  
Takaaki Yonekura ◽  
Munetaka Sugiyama
Keyword(s):  
Mathematical Model ◽  
Mathematical Models ◽  
Computer Simulations ◽  
Inductive Effect ◽  
Inhibitory Effect ◽  
Leaf Primordia ◽  
Leaf Primordium ◽  
Spiral Pattern ◽  
The Mathematical Model ◽  
Mathematical Model Analysis

The view is widely accepted that the inhibitory effect of existing leaf primordia on new primordium formation determines phyllotactic patterning. Previous studies have shown that mathematical models based on such inhibitory effect can generate most of phyllotactic patterns. However, a few types of phyllotaxis still remain unaddressed. A notable example is costoid phyllotaxis showing spiromonostichy, which is characterized by a steep spiral with a small divergence angle and is unique to Costaceae plants. Costoid phyllotaxis has been called a "genuine puzzle" because it seems to disagree with the inhibitory effect-based mechanism. In an attempt to produce a steep spiral pattern, we developed a new mathematical model assuming that each leaf primordium emits not only the inhibitory effect but also some inductive effect. Computer simulations with the new model successfully generated a steep spiral pattern when these two effects met a certain relationship. The obtained steep spiral matched the real costoid phyllotaxis observed with Costus megalobractea. We also found by the mathematical model analysis that the early phyllotactic transition in the seedlings of this plant can be explained by the SAM enlargement.

scholarly journals γ-Hydroxybutyrate does not mediate glucose inhibition of glucagon secretion

2020 ◽  
Vol 295 (16) ◽  
pp. 5419-5426
Author(s):  
Qian Yu ◽  
Bao Khanh Lai ◽  
Parvin Ahooghalandari ◽  
Anders Helander ◽  
Erik Gylfe ◽  
...  
Keyword(s):  
Glucagon Secretion ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Human Islets ◽  
Glucagon Release ◽  
Paracrine Factors ◽  
Glucose Inhibition ◽  
Mouse Islets ◽  
Blood Glucose Concentrations ◽  
Effect Of Glucose

Hypersecretion of glucagon from pancreatic α-cells strongly contributes to diabetic hyperglycemia. Moreover, failure of α-cells to increase glucagon secretion in response to falling blood glucose concentrations compromises the defense against hypoglycemia, a common complication in diabetes therapy. However, the mechanisms underlying glucose regulation of glucagon secretion are poorly understood and likely involve both α-cell–intrinsic and intraislet paracrine signaling. Among paracrine factors, glucose-stimulated release of the GABA metabolite γ-hydroxybutyric acid (GHB) from pancreatic β-cells might mediate glucose suppression of glucagon release via GHB receptors on α-cells. However, the direct effects of GHB on α-cell signaling and glucagon release have not been investigated. Here, we found that GHB (4–10 μm) lacked effects on the cytoplasmic concentrations of the secretion-regulating messengers Ca2+ and cAMP in mouse α-cells. Glucagon secretion from perifused mouse islets was also unaffected by GHB at both 1 and 7 mm glucose. The GHB receptor agonist 3-chloropropanoic acid and the antagonist NCS-382 had no effects on glucagon secretion and did not affect stimulation of secretion induced by a drop in glucose from 7 to 1 mm. Inhibition of endogenous GHB formation with the GABA transaminase inhibitor vigabatrin also failed to influence glucagon secretion at 1 mm glucose and did not prevent the suppressive effect of 7 mm glucose. In human islets, GHB tended to stimulate glucagon secretion at 1 mm glucose, an effect mimicked by 3-chloropropanoic acid. We conclude that GHB does not mediate the inhibitory effect of glucose on glucagon secretion.

Insulin as a physiological modulator of glucagon secretion

2008 ◽  
Vol 295 (4) ◽  
pp. E751-E761 ◽  
Author(s):  
Pritpal Bansal ◽  
Qinghua Wang
Keyword(s):  
Insulin Secretion ◽  
Blood Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucagon Secretion ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Β Cells ◽  
Receptor System ◽  
Glucose Levels

Glucose homeostasis is regulated primarily by the opposing actions of insulin and glucagon, hormones that are secreted by pancreatic islets from β-cells and α-cells, respectively. Insulin secretion is increased in response to elevated blood glucose to maintain normoglycemia by stimulating glucose transport in muscle and adipocytes and reducing glucose production by inhibiting gluconeogenesis in the liver. Whereas glucagon secretion is suppressed by hyperglycemia, it is stimulated during hypoglycemia, promoting hepatic glucose production and ultimately raising blood glucose levels. Diabetic hyperglycemia occurs as the result of insufficient insulin secretion from the β-cells and/or lack of insulin action due to peripheral insulin resistance. Remarkably, excessive secretion of glucagon from the α-cells is also a major contributor to the development of diabetic hyperglycemia. Insulin is a physiological suppressor of glucagon secretion; however, at the cellular and molecular levels, how intraislet insulin exerts its suppressive effect on the α-cells is not very clear. Although the inhibitory effect of insulin on glucagon gene expression is an important means to regulate glucagon secretion, recent studies suggest that the underlying mechanisms of the intraislet insulin on suppression of glucagon secretion involve the modulation of KATP channel activity and the activation of the GABA-GABAA receptor system. Nevertheless, regulation of glucagon secretion is multifactorial and yet to be fully understood.

Calcitonin modulation of insulin and glucagon secretion in man

1982 ◽  
Vol 242 (3) ◽  
pp. E206-E213 ◽  
Author(s):  
D. Giugliano ◽  
N. Passariello ◽  
S. Sgambato ◽  
R. Torella ◽  
F. D'Onofrio
Keyword(s):  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Insulin Response ◽  
Glucagon Secretion ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Acute Insulin Response ◽  
Insulin Responses ◽  
Effect Of Glucose

These studies were undertaken to evaluate the effect of different doses of calcitonin on insulin and glucagon responses to intravenous glucase loads and to assess the mechanism/s by which calcitonin inhibits insulin secretion in man. In our studies, even the infusion of the 1-U dose of calcitonin was found to inhibit by 45% the acute insulin response to a glucose (20 g) pulse. This effect was associated with a significant decrease in glucose disappearance rates. These negative effects of calcitonin on both insulin secretion and glucose tolerance were dose-related. The inhibition of the acute insulin response to glucose was 65% and up to 90% with the infusion of the 4- and 8-U doses, respectively. The suppressive effect of glucose on glucagon secretion was significantly reduced by calcitonin. The inhibitory effect of calcitonin on insulin responses to glucose (5 g) and glucose tolerance was reversed by both theophylline and calcium. By contrast, infusion of lysine acetylsalicylate to block the synthesis of endogenous prostaglandins did not diminish the inhibitory effect of calcitonin on insulin secretion. These results demonstrate that a) calcitonin inhibits glucose-induced insulin responses and deteriorates glucose tolerance in normal humans in a dose-dependent manner; b) calcitonin reduces the suppressive effect of glucose on glucagon secretion in a dose-related fashion; and c) both theophylline and calcium reverse the inhibitory effect of calcitonin on insulin secretion. It is hypothesized that calcitonin effects on insulin and glucagon release are mediated via a change in calcium redistribution in the islet cells.

A mathematical model and an algorithm for sampling sets of components on the Assembly enterprises of space technology

2018 ◽  
Vol 15 (1) ◽  
pp. 39-55
Author(s):  
V. B. Rudakov ◽  
V. M. Makarov ◽  
M. I. Makarov
Keyword(s):  
Mathematical Model ◽  
Mathematical Models ◽  
Space Technology ◽  
Economic Costs ◽  
Problem Statement ◽  
Optimal Plan ◽  
Product Mix ◽  
Technical Parameters ◽  
Complex Products ◽  
Assembly Plants

The article considers the problem of determining the rational plans of the input sampling reliability and technical parameters of components of space technology, the totality of which is supplied to the Assembly plants for the manufacture of complex products of space technology. Problem statement and mathematical model based on the minimization of the economic costs of control and losses related to the risks of taking wrong decisions, are given in the article. The properties of the mathematical models are investigated, the algorithm for its optimization is developed. The result is an optimal plan for the sampling of sets of components, which includes: an optimal product mix subject to mandatory control of the aggregate and optimum risks of first and second kind, when acceptance number of statistical plan is zero. The latter circumstance is due to the high requirements of reliability and technical parameters of products of space technology.

scholarly journals Characterization of potassium channels in pancreatic β cells from ob /ob mice

FEBS Letters ◽  
1990 ◽  
Vol 266 (1-2) ◽  
pp. 105-108 ◽  
Author(s):  
Manuel Kukuljan ◽  
Min Yi Li ◽  
Illani Atwater
Keyword(s):  
Potassium Channels ◽  
Β Cells ◽  
Pancreatic Β Cells

Rapid determination of glomerular filtration rate by single-bolus inulin: a comparison of estimation analyses

1998 ◽  
Vol 84 (6) ◽  
pp. 2154-2162 ◽  
Author(s):  
Cord Sturgeon ◽  
Albert D. Sam ◽  
William R. Law
Keyword(s):  
Mathematical Model ◽  
Glomerular Filtration Rate ◽  
Mathematical Models ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Rapid Determination ◽  
Constant Infusion ◽  
Sprague Dawley ◽  
Single Bolus ◽  
Sprague Dawley Rats

Rapid measurement of glomerular filtration rate (GFR) by an inulin single-bolus technique would be useful, but its accuracy has been questioned. We hypothesized that reported inaccuracies reflect the use of inappropriate mathematical models. GFR was measured in 14 intact and 5 unilaterally nephrectomized conscious male Sprague-Dawley rats (mean weight 368 ± 12 g) by both single-bolus (25 mg/kg) and constant-infusion techniques (0.693 mg ⋅ kg−1 ⋅ min−1). The temporal decline in plasma inulin concentration was analyzed through biexponential curve fitting, which accounted for renal inulin loss before complete vascular and interstitial mixing. We compared our mathematical model based on empirical rationale with those of other investigators whose studies suggest inaccuracy of single-bolus methods. Our mathematical model yielded GFR values by single bolus that agreed with those obtained by constant infusion [slope = 0.94 ± 0.16 (SE); y intercept = 0.23 ± 0.64; r = 0.82]. In comparison to the data obtained by constant inulin infusion, this method yielded a very small bias of −0.0041 ± 0.19 ml/min. Two previously reported models yielded unsatisfactory values (slope = 1.46 ± 0.34, y intercept = 0.47 ± 1.5, r = 0.72; and slope = 0.17 ± 1.26, y intercept = 17.15 ± 5.14, r = 0.03). The biases obtained by using these methods were −2.21 ± 0.42 and −13.90 ± 1.44 ml/min, respectively. The data indicate that when appropriate mathematical models are used, inulin clearance after single-bolus delivery can be used to measure GFR equivalent to that obtained by constant infusion of inulin. Attempts to use methods of analysis for simplicity or expediency can result in unacceptable measurements relative to the clinical range of values seen.

Similar effects by valine and isoleucine on threonine deaminase

1970 ◽  
Vol 48 (7) ◽  
pp. 812-815 ◽  
Author(s):  
W. M. Harding ◽  
J. A. Tubbs ◽  
Deborah McDaniel
Keyword(s):  
Inhibitory Effect ◽  
Effective Inhibitor ◽  
Threonine Deaminase ◽  
Apparent Increase ◽  
Separate Site ◽  
Do So

Isoleucine is known to be a very effective inhibitor and stabilizer of threonine deaminase. In contrast, valine has been reported to be a positive effector for the enzyme by action on a separate site. However, the apparent increase in activity caused by valine is due to stabilization of the enzyme. When stabilization is accomplished by other means, valine exerts only an inhibitory effect. Thus, valine, like isoleucine, both stabilizes and inhibits threonine deaminase and may well do so via the isoleucine site on the enzyme.

Twin Models

1970 ◽  
Vol 19 (1-2) ◽  
pp. 141-141
Author(s):  
L. Gedda ◽  
G. Brenci ◽  
M. T. Lun
Keyword(s):  
Mathematical Model ◽  
Mathematical Models ◽  
Genetic Parameters ◽  
Simultaneous Recording ◽  
Theoretical Relationship ◽  
Twin Models

The theoretical relationship between the distribution of a given trait in a population of twin pairs and several genetic parameters has been examined. In particular, a series of mathematical models has been worked out, that, when applied to a twin population, nonselected for the occurrence of a given trait and nondiagnosed as to zygosity, leads to an estimate of:1) The MZ: DZ ratio in the population;2) The frequency of the genotype responsible for a given trait;3) The probability of manifestation of the trait;4) The value of epistatic factors.A further mathematical model affords the estimate of linkage in the hypothesis of simultaneous recording of more than one trait.

Numerical modelling of swirling momentumless turbulent wake dynamics

2018 ◽  
pp. 37-48
Author(s):  
Андрей Геннадьевич Деменков ◽  
Геннадий Георгиевич Черных
Keyword(s):  
Numerical Simulation ◽  
Mathematical Model ◽  
Mathematical Models ◽  
Equations Of Motion ◽  
Turbulent Wake ◽  
The Body ◽  
Jet Flows ◽  
Reynolds Stresses ◽  
Bodies Of Revolution ◽  
Averaged Equations

С применением математической модели, включающей осредненные уравнения движения и дифференциальные уравнения переноса нормальных рейнольдсовых напряжений и скорости диссипации, выполнено численное моделирование эволюции безымпульсного закрученного турбулентного следа с ненулевым моментом количества движения за телом вращения. Получено, что начиная с расстояний порядка 1000 диаметров от тела течение становится автомодельным. На основе анализа результатов численных экспериментов построены упрощенные математические модели дальнего следа. Swirling turbulent jet flows are of interest in connection with the design and development of various energy and chemical-technological devices as well as both study of flow around bodies and solving problems of environmental hydrodynamics, etc. An interesting example of such a flow is a swirling turbulent wake behind bodies of revolution. Analysis of the known works on the numerical simulation of swirling turbulent wakes behind bodies of revolution indicates lack of knowledge on the dynamics of the momentumless swirling turbulent wake. A special case of the motion of a body with a propulsor whose thrust compensates the swirl is studied, but there is a nonzero integral swirl in the flow. In previous works with the participation of the authors, a numerical simulation of the initial stage of the evolution of a swirling momentumless turbulent wake based on a hierarchy of second-order mathematical models was performed. It is shown that a satisfactory agreement of the results of calculations with the available experimental data is possible only with the use of a mathematical model that includes the averaged equations of motion and differential equations for the transfer of normal Reynolds stresses along the rate of dissipation. In the present work, based on the above mentioned mathematical model, a numerical simulation of the evolution of a far momentumless swirling turbulent wake with a nonzero angular momentum behind the body of revolution is performed. It is shown that starting from distances of the order of 1000 diameters from the body the flow becomes self-similar. Based on the analysis of the results of numerical experiments, simplified mathematical models of the far wake are constructed. The authors dedicate this work to the blessed memory of Vladimir Alekseevich Kostomakha.

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