Predicting Blood Glucose Levels

[Drew Alessi]

Hi Everyone,

I am trying to predict the blood levels of glucose (and a few other metabolites) using the whole-body model under a given diet. How do you recommend to do this?

 

On a related note, I wonder if glucose in the blood compartment, "glc_D[bc]", is under steady-state mass balance. When I sum the flux of all reactions in which "glc_D[bc]" appears as a reactant or product, times it's stoichiometric coeff. I get a value in the order of -3.05E-05, which is not close enough to zero implying that maybe the steady-state mass balance is not imposed for it (simulations under EU average diet). This happens for other metabolites I tested too.

 

Thank you in advance.

Best Regards,

Drew

[Ines Thiele]

Hi Drew

Which solver are you using?

With iLog cplex:

MALE

QP:

param.minNorm = 1e-6;
FBA = optimizeWBModel(male,param)

male.S(ismember(male.mets,'glc_D[bc]'),:)*FBA.v
answer: 3.3143e-11

LP:
FBA = optimizeWBModel(male)
male.S(ismember(male.mets,'glc_D[bc]'),:)*FBA.v

answer:  2.0712e-11

FEMALE

QP:
param.minNorm = 1e-6;
FBAf = optimizeWBModel(female,param)

female.S(ismember(female.mets,'glc_D[bc]'),:)*FBAf.v
answer:    6.3955e-10

LP:
FBAf = optimizeWBModel(female)

female.S(ismember(female.mets,'glc_D[bc]'),:)*FBAf.v

answer:   7.6712e-11

Ines

------
Ines Thiele, PhD
Professor in Systems Biomedicine
ERC grant recipient
University of Galway Foundation Research Leadership Programme Awardee
Principal Investigator, APC Microbiome Ireland 

Principal Investigator, Ryan Institute

Principal Investigator, Galway Neuroscience Centre

University of Galway
School of Medicine
School of Biological and Chemical Sciences | Microbiology, 

Orbsen Building | Galway, Ireland

thielelab.eu,
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[Drew Alessi]

Thanks for this feedback. It sounded like I had some solver issues, which I was able to resolve, and now I am able to get the same solutions as yours. Nevertheless, since all metabolites in the blood compartment are under the steady-state mass balance, I still wonder if there is any way of predicting the serum levels of glucose and other metabolites using the WBM (without performing dynamic simulations).

Best,

Drew Alessi

[Ines Thiele]

Here is one example of how to achieve this

Dynamic flux balance analysis of whole-body metabolism for type 1 diabetes: https://www.nature.com/articles/s43588-021-00074-3

Ines

------
Ines Thiele, PhD
Professor in Systems Biomedicine
ERC grant recipient
University of Galway Foundation Research Leadership Programme Awardee
Principal Investigator, APC Microbiome Ireland 

Principal Investigator, Ryan Institute

Principal Investigator, Galway Neuroscience Centre

University of Galway
School of Medicine
School of Biological and Chemical Sciences | Microbiology, 

Orbsen Building | Galway, Ireland

thielelab.eu,
GoogleScholarProfile,
Follow me on Twitter

CONFIDENTIALITY.  The content of this email (including any attachment(s)), is/are confidential and may be privileged and is intended for the addressee only. Any reader of this message who is not the intended recipient is notified that any dissemination, distribution or copying of this communication is prohibited. If you receive this communication in error, please notify me immediately and please also delete all copies from your computer system. Thank you for your co-operation.

To view this discussion on the web visit https://groups.google.com/d/msgid/cobra-toolbox/3f8a154a-76b5-4302-8d9c-ab1d428cafban%40googlegroups.com.

[Drew Alessi]

Thanks for the quick response! Yes, I was aware of this paper and will look into it further, but I referring to predicting serum levels of metabolites using steady-state simulations (that’s what I meant by “without doing dynamic simulations.” Does your response mean that we cannot do this using steady-state simulations and have to use dynamic FBA? 

[Drew Alessi]

Hi,

I just wanted to say thank you again for getting back to me with this helpful example and insightful paper. I'm still unsure whether or not it is feasible to predict the serum levels of glucose and other metabolites using the WBM (without performing dynamic simulations). Thank you in advance!