In-silico modelling of insulin secretion and pancreatic beta-cell function for clinical applications: is it worth the effort?

Abstract

Introduction: Recently, there has been ongoing dialogue with clinical researchers about the practical benefits of in-silico mathematical modelling in studying glucose metabolism. In fact, several in-silico models have been developed in such field, as outlined by some review studies (1–4). Among the different metabolic processes addressed by such models, one relevant is insulin secretion and pancreatic beta-cell function. Indeed, although it is currently known that several factors affect glucose homeostasis (5), the impairment in insulin secretion/betacell function, in addition to that of insulin sensitivity, are typically the most important determinants of glycemic control deterioration and possible development of type 2 diabetes. In this opinion article, we will provide considerations about in-silico modelling of beta-cell function. Some models of beta-cell function describe aspects of such process at molecular or cellular level (6–13). These models are useful to get further insights in relevant molecular/ cellular mechanisms, and in addition they can stimulate new experimental research activity in an in-vitro context. Other models are instead oriented to describe insulin secretion/betacell function at whole body level, and these models are those typically having potential for clinical applications (14–17). In some of the following paragraphs, we focus on the main characteristics and findings of the model by Mari et al. (17). This model has been applied in the clinical context for the analysis of thousands of glucose tolerance tests, including those in wide multicenter projects (such as the IMI-DIRECT Project), focused on longitudinal study of participants with both type 2 diabetes (T2D) (18) and impaired glucose regulation, but also normal glucose tolerance (19). The model by Mari et al. (17) describes three main processes of beta-cell function: the glucose-insulin dose-response relation (“DR” component), the early insulin secretion (“E” component), and the insulin secretion potentiation (“P” component”). We succinctly describe those characteristics in the next section. For brevity, we refer to the model as the DR-EP model.