Putting the pieces together in diabetes research: towards a hierarchical model of whole-body glucose homeostasis.
Type 2 diabetes is one of the most widespread and rapidly spreading diseases world-wide and has been subject of extensive research efforts. However, understanding the molecular basis of the disease is increasing piecemeal and a consensus regarding the overall picture of normal metabolic regulation and malfunction in diabetes has not emerged. A systems biology approach, combining mathematical modelling with simultaneous high-throughput measurements, can be of considerable help. On the whole-body level, this has been done in pharmacokinetic and pharmacodynamic models, which recently have started to mature into more physiologically realistic organ-based models. At the other end of the spectrum, detailed models for crucial cellular processes are starting to mature into complete modules that potentially can be fitted into such whole-body organ-based models. The result of such a merge is a multi-level hierarchical model, which is a model type that has been common in technical systems. In this review, we report and exemplify some of the recent progress that has been made to achieve such a hierarchical model, and we argue why it is only through such a model that a complete picture of diabetes mellitus can be obtained.
Cedersund
Gunnar
G
Department of Clinical and Experimental Medicine, Cell Biology and Diabetes Research Centre, Linköping University, Linköping, Sweden. gunnar@ibk.liu.se
Strålfors
Peter
P
D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D015233:Models, Statistical; D010179:Pancreas / Q000473:pathology
D007004:Hypoglycemic Agents; D005947:Glucose