Blood glucose regulation by an organ-based multi-level model

Husna, Amity University Kolkata

The process of regulation of glucose in our blood at a steady-state is known as glucose homeostasis. This regulation is very important as long-lasting disturbances in the blood sugar concentration can cause both type 1 and type 2 diabetes mellitus (T2D) and other fatal diseases. To understand this complexity of blood glucose control system, a mathematical model was developed. But due to its malfunction in fatal diseases like diabetes, new insights have been introduced from the intra-cellular level to a wide whole-body perspective.

 In type 1 diabetes, the insulin-producing beta-cells are destroyed by the immune system and it is treated via injections or insulin pumps. In T2D, the patient has both a reduced capacity to produce insulin and has developed insulin resistance. This resistance spread to the organs in ways which are not fully understood. So, recently an updated multi-level model has been developed which can understand this complex interaction. It provides more accurate information of how much glucose is being taken up by different organs and the interactions between glucose and insulin with various organs in response to a meal. 

This model has resolved three critical issues regarding the role of each metabolically active organ in glucose uptake. In this model, the liver is a glucose-utilizing organ which was only considered as glucose producing organ in the previous model. The addition of glucose uptake in the liver is the most important part of this model because the liver takes up the most glucose of our body. Secondly, the timing difference between the glucose uptake of muscle and adipose tissue in response to a meal is also included. Thirdly, the model has been updated to include the impact of blood flow on glucose uptake in adipose tissue. Finally, these three improvements have been merged together to build an updated multi-level model. Hence, this model provides the most comprehensive description of the multi-level roles that each organ plays in glucose homeostasis in humans and it’s also a useful model for integration of future data for particular sub-systems.

Also read: Structural and Functional Inhibition of CHIKV by CHK-124 and CHK-263mAbs

 SOURCE: An organ-based multi-level model for glucose homeostasis: organ distributions, timing, and impact of blood flow, Tilda Herrgardh, Hao Li,  Elin Nyman,  Gunnar Cedersund https://www.biorxiv.org/content/10.1101/2020.10.21.344499v1?rss=1

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