Multiscale modelling of insulin secretion during an intravenous glucose tolerance test

Pedersen, Morten Gram; Cobelli, Claudio

doi:10.1098/rsfs.2012.0085

Cited by 8 publications

(5 citation statements)

References 25 publications

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“…Extensions of the previously cited work by Pedersen et al [ 18 ] have been presented in successive works again by Pedersen et al [ 46 , 47 ] for meal ingestion and IVGTT. In a recent work by Pedersen and Cobelli [ 47 ], a slight modification in the potentiation mechanism was introduced, with the aim to make the model consistent with available top-down models of insulin secretion. The consequence is that during the IVGTT the glycemia time-derivative term may be neglected.…”

Section: Pancreatic Insulin Secretion: Experiments and Modelingmentioning

confidence: 87%

A Unifying Organ Model of Pancreatic Insulin Secretion

et al. 2015

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The secretion of insulin by the pancreas has been the object of much attention over the past several decades. Insulin is known to be secreted by pancreatic β-cells in response to hyperglycemia: its blood concentrations however exhibit both high-frequency (period approx. 10 minutes) and low-frequency oscillations (period approx. 1.5 hours). Furthermore, characteristic insulin secretory response to challenge maneuvers have been described, such as frequency entrainment upon sinusoidal glycemic stimulation; substantial insulin peaks following minimal glucose administration; progressively strengthened insulin secretion response after repeated administration of the same amount of glucose; insulin and glucose characteristic curves after Intra-Venous administration of glucose boli in healthy and pre-diabetic subjects as well as in Type 2 Diabetes Mellitus. Previous modeling of β-cell physiology has been mainly directed to the intracellular chain of events giving rise to single-cell or cell-cluster hormone release oscillations, but the large size, long period and complex morphology of the diverse responses to whole-body glucose stimuli has not yet been coherently explained. Starting with the seminal work of Grodsky it was hypothesized that the population of pancreatic β-cells, possibly functionally aggregated in islets of Langerhans, could be viewed as a set of independent, similar, but not identical controllers (firing units) with distributed functional parameters. The present work shows how a single model based on a population of independent islet controllers can reproduce very closely a diverse array of actually observed experimental results, with the same set of working parameters. The model’s success in reproducing a diverse array of experiments implies that, in order to understand the macroscopic behaviour of the endocrine pancreas in regulating glycemia, there is no need to hypothesize intrapancreatic pacemakers, influences between different islets of Langerhans, glycolitic-induced oscillations or β-cell sensitivity to the rate of change of glycemia.

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Section: Pancreatic Insulin Secretion: Experiments and Modelingmentioning

confidence: 87%

A Unifying Organ Model of Pancreatic Insulin Secretion

et al. 2015

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“…Current models of the pathogenesis of diabetes typically place the feedback interactions between glucose and insulin at the core of glycaemic control ( 17, 25 ). While these models assume that blood glucose uptake into cells directly depends on circulating levels of insulin, the mechanisms by which insulin regulates transmembrane glucose transport have not been explicitly modelled.…”

Section: Methodsmentioning

confidence: 99%

Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease

Zavala

Gil-Gómez

Wedgwood

et al. 2020

Preprint

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25A systems level coordination of physiological rhythms is essential to sustain healthy states, especially in 26 the face of stimuli that may disrupt such rhythms. The timing of meals, medication and chronic stress 27 can profoundly influence metabolism, which depends on the dynamic interactions between glucose, 28 insulin and cortisol. Although the metabolic and stress endocrine axes are simultaneously disrupted in 29 many diseases, a theoretical framework to understand how chronodisruption leads to disease is lacking. 30 By developing a mathematical model of glucose utilisation that accounts for the antagonism between 31 insulin and cortisol, we investigate the dynamic effects of glucose boluses under normal and disrupted 32 cortisol rhythms, including the effects of cortisol agonists and antagonists. We also predict how cortisol 33 rhythms modulate circadian responses to oral glucose diagnostic tests, and analyse the disruptions 34 caused by hypercortisolism. Finally, we predict the mechanisms leading to type 2 diabetes in patients 35 with normal and excess cortisol. 36 37 38 39 40 41 42 43 157

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“…It is now clear from the various sophisticated mouse models used in the different studies that local glucagon signaling is required for appropriate insulin secretion, to preserve glucose tolerance during the metabolic stress induced by high-fat feeding, and to maintain proper glucose homeostasis in vivo ( 36 – 38 ). That previous studies using ablation of α-cells failed to show this important intraislet cross talk is probably due to the deployment of compensatory mechanisms or to an incomplete reduction in α-cells ( 44 ).…”

Section: The Role Of Glucagon As a Paracrine Signalmentioning

confidence: 95%

The Local Paracrine Actions of the Pancreatic α-Cell

et al. 2019

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Secretion of glucagon from the pancreatic α-cells is conventionally seen as the first and most important defense against hypoglycemia. Recent findings, however, show that α-cell signals stimulate insulin secretion from the neighboring β-cell. This article focuses on these seemingly counterintuitive local actions of α-cells and describes how they impact islet biology and glucose metabolism. It is mostly based on studies published in the last decade on the physiology of α-cells in human islets and incorporates results from rodents where appropriate. As this and the accompanying articles show, the emerging picture of α-cell function is one of increased complexity that needs to be considered when developing new therapies aimed at promoting islet function in the context of diabetes.

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Multiscale modelling of insulin secretion during an intravenous glucose tolerance test

Cited by 8 publications

References 25 publications

A Unifying Organ Model of Pancreatic Insulin Secretion

A Unifying Organ Model of Pancreatic Insulin Secretion

Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease

The Local Paracrine Actions of the Pancreatic α-Cell

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