| 1. |
- Marinković, Tijana, et al.
(författare)
-
Integrated model of metabolism and autoimmune response in β-cell death and progression to type 1 diabetes
- 2012
-
Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:12
-
Tidskriftsartikel (refereegranskat)abstract
- Progression to type 1 diabetes is characterized by complex interactions of environmental, metabolic and immune system factors, involving both degenerative pathways leading to loss of pancreatic β-cells as well as protective pathways. The interplay between the degenerative and protective pathways may hold the key to disease outcomes, but no models have so far captured the two together. Here we propose a mathematical framework, an ordinary differential equation (ODE) model, which integrates metabolism and the immune system in early stages of disease process. We hypothesize that depending on the degree of regulation, autoimmunity may also play a protective role in the initial response to stressors. We assume that β-cell destruction follows two paths of loss: degenerative and autoimmune-induced loss. The two paths are mutually competing, leading to termination of the degenerative loss and further to elimination of the stress signal and the autoimmune response, and ultimately stopping the β-cell loss. The model describes well our observations from clinical and non-clinical studies and allows exploration of how the rate of β-cell loss depends on the amplitude and duration of autoimmune response.
|
|
| 2. |
- Marinković, Tijana, et al.
(författare)
-
Modeling strategies to study metabolic pathways in progression to type 1 diabetes : Challenges and opportunities
- 2016
-
Ingår i: Archives of Biochemistry and Biophysics. - Maryland Heights, MO, USA : Academic Press. - 0003-9861 .- 1096-0384. ; 589, s. 131-7
-
Forskningsöversikt (refereegranskat)abstract
- Seroconversion to islet autoimmunity is preceded by metabolic disturbances in children who later progress to overt type 1 diabetes (T1D). The underlying metabolic pathways and the interaction of metabolic and immune system factors involved in progression to the disease are however poorly understood. There is a clear need for mathematical models which capture the temporal and spatial complexity of early pathogenesis of T1D. Here we review the early attempts to model the development of islet autoimmunity and T1D, including the models which emphasize the potential beneficial role of autoimmune response in specific circumstances, such as to 'correct' for the early metabolic disturbances. We also highlight the genome-scale metabolic modeling as a promising new avenue to study metabolism and its interactions with the immune system in T1D.
|
|
