scholarly journals An organ-based multi-level model for glucose homeostasis: organ distributions, timing, and impact of blood flow

2020 ◽  
Author(s):  
Tilda Herrgårdh ◽  
Hao Li ◽  
Elin Nyman ◽  
Gunnar Cedersund
Keyword(s):  
Blood Flow ◽  
Glucose Homeostasis ◽  
Statistical Tests ◽  
Cellular Level ◽  
Whole Body ◽  
Response Curves ◽  
Future Data ◽  
Level Model ◽  
Multi Level ◽  
Original Cell

AbstractGlucose homeostasis is the tight control of glucose in the blood. This complex control is important and not yet sufficiently understood, due to its malfunction in serious diseases like diabetes. Due to the involvement of numerous organs and sub-systems, each with their own intra-cellular control, we have developed a multi-level mathematical model, for glucose homeostasis, which integrates a variety of data. Over the last 10 years, this model has been used to insert new insights from the intra-cellular level into the larger whole-body perspective. However, the original cell-organ-body translation has during these years never been updated, despite several critical shortcomings, which also have not been resolved by other modelling efforts. For this reason, we here present an updated multi-level model. This model provides a more accurate sub-division of how much glucose is being taken up by the different organs. Unlike the original model, we now also account for the different dynamics seen in the different organs. The new model also incorporates the central impact of blood flow on insulin-stimulated glucose uptake. Each new improvement is clear upon visual inspection, and they are also supported by statistical tests. The final multi-level model describes >300 data points in >40 time-series and dose-response curves, resulting from a large variety of perturbations, describing both intra-cellular processes, organ fluxes, and whole-body meal responses. We hope that this model will serve as an improved basis for future data integration, useful for research and drug developments within diabetes.

scholarly journals An Updated Organ-Based Multi-Level Model for Glucose Homeostasis: Organ Distributions, Timing, and Impact of Blood Flow

2021 ◽  
Vol 12 ◽  
Author(s):  
Tilda Herrgårdh ◽  
Hao Li ◽  
Elin Nyman ◽  
Gunnar Cedersund
Keyword(s):  
Blood Flow ◽  
Glucose Homeostasis ◽  
Statistical Tests ◽  
Cellular Level ◽  
Whole Body ◽  
Response Curves ◽  
Future Data ◽  
Level Model ◽  
Multi Level ◽  
Original Cell

Glucose homeostasis is the tight control of glucose in the blood. This complex control is important, due to its malfunction in serious diseases like diabetes, and not yet sufficiently understood. Due to the involvement of numerous organs and sub-systems, each with their own intra-cellular control, we have developed a multi-level mathematical model, for glucose homeostasis, which integrates a variety of data. Over the last 10 years, this model has been used to insert new insights from the intra-cellular level into the larger whole-body perspective. However, the original cell-organ-body translation has during these years never been updated, despite several critical shortcomings, which also have not been resolved by other modeling efforts. For this reason, we here present an updated multi-level model. This model provides a more accurate sub-division of how much glucose is being taken up by the different organs. Unlike the original model, we now also account for the different dynamics seen in the different organs. The new model also incorporates the central impact of blood flow on insulin-stimulated glucose uptake. Each new improvement is clear upon visual inspection, and they are also supported by statistical tests. The final multi-level model describes >300 data points in >40 time-series and dose-response curves, resulting from a large variety of perturbations, describing both intra-cellular processes, organ fluxes, and whole-body meal responses. We hope that this model will serve as an improved basis for future data integration, useful for research and drug developments within diabetes.

scholarly journals A closed-loop multi-level model of glucose homeostasis

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0190627 ◽  
Author(s):  
Cansu Uluseker ◽  
Giulia Simoni ◽  
Luca Marchetti ◽  
Marco Dauriz ◽  
Alice Matone ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Closed Loop ◽  
Level Model ◽  
Multi Level

The Role of Time in Health IoT

2017 ◽  
pp. 197-213
Author(s):  
Lambert Spaanenburg
Keyword(s):  
Blood Flow ◽  
Network Architecture ◽  
Blood Pressure Measurement ◽  
The Body ◽  
New Device ◽  
Non Invasive ◽  
Body Change ◽  
Level Model ◽  
Multi Level

As the biological processes in the body change constantly, comparable measurements should be taken simultaneously in time and place. In practice, this is hard to achieve. Synchronicity is required to certify medical accuracy for a new device by reference to a certified one. In a typical health IoT, synchronicity cannot be enforced procedurally and timing needs to be part of the network architecture. Popular examples are in blood pressure measurement. Putting the blood flow in a known pinch-off situation performs synchronization. But this principle cannot be extended to other non-invasive measurements. Hence the chapter proposes to synchronize on basis of the heart rate extracted from the blood flow at arbitrary positions on the body. This models the blood flow in the body and relates all to the rhythm of the heart. It brings existing phenomena into a single, multi-level model that allows wireless networked wearables into a single health-monitoring scheme.

scholarly journals Glucose transporters in the 21st Century

2010 ◽  
Vol 298 (2) ◽  
pp. E141-E145 ◽  
Author(s):  
Bernard Thorens ◽  
Mike Mueckler
Keyword(s):  
21St Century ◽  
Glucose Homeostasis ◽  
Mammalian Cells ◽  
Glucose Transporter ◽  
Cellular Level ◽  
Transport Proteins ◽  
Whole Body ◽  
Kinetic Properties ◽  
Membrane Transport Proteins ◽  
Physiological Substrates

The ability to take up and metabolize glucose at the cellular level is a property shared by the vast majority of existing organisms. Most mammalian cells import glucose by a process of facilitative diffusion mediated by members of the Glut (SLC2A) family of membrane transport proteins. Fourteen Glut proteins are expressed in the human and they include transporters for substrates other than glucose, including fructose, myoinositol, and urate. The primary physiological substrates for at least half of the 14 Glut proteins are either uncertain or unknown. The well-established glucose transporter isoforms, Gluts 1–4, are known to have distinct regulatory and/or kinetic properties that reflect their specific roles in cellular and whole body glucose homeostasis. Separate review articles on many of the Glut proteins have recently appeared in this journal. Here, we provide a very brief summary of the known properties of the 14 Glut proteins and suggest some avenues of future investigation in this area.

Effects of epinephrine on insulin-mediated glucose uptake in whole body and leg muscle in humans: role of blood flow

1992 ◽  
Vol 263 (2) ◽  
pp. E199-E204 ◽  
Author(s):  
M. Laakso ◽  
S. V. Edelman ◽  
G. Brechtel ◽  
A. D. Baron
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Dose Response ◽  
Insulin Dose ◽  
Whole Body ◽  
Response Curves ◽  
Leg Muscle

In vivo insulin-mediated glucose uptake (IMGU) occurs chiefly in skeletal muscle, where it is determined by the product of arteriovenous glucose difference (delta AVG) and blood flow (BF) rate into muscle. Epinephrine (Epi) reduces the rate of IMGU in whole body. To examine whether this is due to a reduction in delta AVG across or BF into skeletal muscle we constructed insulin dose-response curves for whole body IMGU and leg muscle IMGU- using euglycemic clamp ((+)[3-3H]glucose infusion) and leg balance techniques during insulin infusions ranging from 10 to 1,200 mU.m-2.min-1. We studied six subjects [wt 70 +/- 2 (SE) kg] during an Epi infusion at a single rate of 0.002 mg.kg-1.min-1 and six subjects (70 +/- 3 kg) during a saline infusion alone. Maximum whole body glucose uptake (WBGU) was similar during Epi and saline infusions [71.4 vs. 73.6 mmol.kg-1.min-1, P = not significant (NS)]. Compared with saline, maximum delta AVG was decreased during Epi infusion (1.04 vs. 1.31 mM, P less than 0.01). Compared with saline alone maximum leg BF was increased (5.3 vs. 4.3 dl/min, P less than 0.01) during Epi infusion. Thus maximum leg glucose uptake (LGU) was similar (696 vs. 821 pmol.leg-1.min-1, P = NS) during infusion of Epi and saline, respectively. Half-maximal effective dose for insulin's effect to stimulate WBGU, delta AVG, BF, and LGU was increased two- to threefold during Epi vs. saline infusions (P less than 0.01 for all values).(ABSTRACT TRUNCATED AT 250 WORDS)

Thermoneutral housing does not influence fat mass or glucose homeostasis in C57BL/6 mice

2018 ◽  
Vol 239 (3) ◽  
pp. 313-324 ◽  
Author(s):  
Lewin Small ◽  
Henry Gong ◽  
Christian Yassmin ◽  
Gregory J Cooney ◽  
Amanda E Brandon
Keyword(s):  
Glucose Metabolism ◽  
Ambient Temperature ◽  
Fat Mass ◽  
Glucose Homeostasis ◽  
Dietary Intervention ◽  
Whole Body ◽  
Housing Temperature ◽  
Brown Adipose ◽  
Normal Chow ◽  
Obesogenic Diet

One major factor affecting physiology often overlooked when comparing data from animal models and humans is the effect of ambient temperature. The majority of rodent housing is maintained at ~22°C, the thermoneutral temperature for lightly clothed humans. However, mice have a much higher thermoneutral temperature of ~30°C, consequently data collected at 22°C in mice could be influenced by animals being exposed to a chronic cold stress. The aim of this study was to investigate the effect of housing temperature on glucose homeostasis and energy metabolism of mice fed normal chow or a high-fat, obesogenic diet (HFD). Male C57BL/6J(Arc) mice were housed at standard temperature (22°C) or at thermoneutrality (29°C) and fed either chow or a 60% HFD for 13 weeks. The HFD increased fat mass and produced glucose intolerance as expected but this was not exacerbated in mice housed at thermoneutrality. Changing the ambient temperature, however, did alter energy expenditure, food intake, lipid content and glucose metabolism in skeletal muscle, liver and brown adipose tissue. Collectively, these findings demonstrate that mice regulate energy balance at different housing temperatures to maintain whole-body glucose tolerance and adiposity irrespective of the diet. Despite this, metabolic differences in individual tissues were apparent. In conclusion, dietary intervention in mice has a greater impact on adiposity and glucose metabolism than housing temperature although temperature is still a significant factor in regulating metabolic parameters in individual tissues.

1971-P: Activation of Adipocyte Gq Signaling Causes Improved Whole-Body Glucose Homeostasis

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1971-P
Author(s):  
TAKEFUMI KIMURA ◽  
SAI PRASAD PYDI ◽  
LEI WANG ◽  
YINGHONG CUI ◽  
OKSANA GAVRILOVA ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Whole Body

An Analysis on Factors of Parent Involvement in Middle School Using Multi-Level Model

2018 ◽  
Vol 18 (5) ◽  
pp. 521-540
Author(s):  
Eunyoung Kim ◽  
◽  
Soonbum Kwon ◽  
Meejung Chin ◽  
◽  
...  
Keyword(s):  
Middle School ◽  
Parent Involvement ◽  
Level Model ◽  
Multi Level

Neural control of glucose uptake by skeletal muscle after central administration of NMDA

1995 ◽  
Vol 268 (2) ◽  
pp. R492-R497 ◽  
Author(s):  
C. H. Lang ◽  
M. Ajmal ◽  
A. G. Baillie
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Neural Control ◽  
Plasma Insulin ◽  
Regional Blood Flow ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Glucose Disposal ◽  
Central Administration

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow.

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