Some insights into an integrative mathematical model

The ambition of this document is to set in evidence the prerequisite for integrative (mathematical) models, mechanism-based models, for appetite/bodyweight control. For achieving this goal, it is provided a scrutinized literature review and it is organized them in such a way to make the point. The quantitative methods exploited by the authors are called differential equations solved numerically; they are discussed briefly since it is not our goal herein to handle details. On the current state of the art, there is no mathematical model to the best of the author’s knowledge targeting at integrating several hormones at once in mathematical descriptions: even for single hormones, the literature is either occasional or do not exist at all; it is depicted some results for simple models already built. As it can be seen, the functions and roles seem fuzzy, most hormones seem to be piloting the same undertaking. The key challenge from a mathematical modeling perspective is how to separate properly the mechanisms of each hormone. The kind of pursuit presented herein could initiate an imperative cascade of mathematical modeling applied to metabolism of bodyweight control and energy homeostasis.

Full text. PDF.

Insulin is Required for Prandial Ghrelin Suppression in Humans

Accumulating evidence indicates that ghrelin plays a role in regulating food intake and energy homeostasis. In normal subjects, circulating ghrelin concentrations decrease after meal ingestion and increase progressively before meals. At present, it is not clear whether nutrients suppress the plasma ghrelin concentration directly or indirectly by stimulating insulin secretion. To test the hypothesis that insulin regulates postprandial plasma ghrelin concentrations in humans, we compared the effects of meal ingestion on plasma ghrelin levels in six C-peptide-negative subjects with type 1 diabetes and in six healthy subjects matched for age, sex, and BMI. In conclusion, 1) insulin is essential for meal-induced plasma ghrelin suppression, 2) basal insulin availability is sufficient for postprandial ghrelin suppression in type 1 diabetic subjects, and 3) lack of meal-induced ghrelin suppression caused by severe insulin deficiency may explain hyperphagia of uncontrolled type 1 diabetic subjects.

Full work: http://www.medscape.com/viewarticle/465766. 

A Mathematical Model for Ghrelin: energy homeostasis and appetite control (poster section)

Ghrelin is a quite powerful hormone discovered in the end of the 1990s that controls appetite and energy homeostasis, alongside leptin and other hormones still to be investigated in depth by the medical sciences literature. 

On this poster we provide a simple mathematical model, consisting of a set of ordinary differential equations detailing ghrelin dynamics combined to stomach and duodenum stretch variations due to meals. Numerical simulations are able to replicate in silico data available from the literature. 

We explain the model and set the new avenues, bearing in mind the model is part of a bigger project whose aim is making sense of glucose control from a “network” (integrative) perspective, “a web of hormones.” 

The main drive of this endeavor is suggesting a primary mathematical model for ghrelin dynamics. And, as a result, the problematic is that no single attempt to gather together several hormones in a single depiction seems to be existent (or important enough). 

Bearing in mind the model is the first attempt and several challenges still must be tackled, we shall use the second part of the poster for discussing these problematics and how we intend to solve them. 

Finally, our model is what can be called “white box,” i.e. mechanism-based model, which means that for us it is chased a model which is physiologically reasonable rather than just replicating experimental results. All the results provided are in silico, in vivo and in vitro results are taken from the literature.

See poster.