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- Choy, Steve, 1987-
(författare)
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Semi-mechanistic models of glucose homeostasis and disease progression in type 2 diabetes
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by consistently high blood glucose, resulting from a combination of insulin resistance and reduced capacity of β-cells to secret insulin. While the exact causes of T2DM is yet unknown, obesity is known to be a major risk factor as well as co-morbidity for T2DM. As the global prevalence of obesity continues to increase, the association between obesity and T2DM warrants further study. Traditionally, mathematical models to study T2DM were mostly empirical and thus fail to capture the dynamic relationship between glucose and insulin. More recently, mechanism-based population models to describe glucose-insulin homeostasis with a physiological basis were proposed and offered a substantial improvement over existing empirical models in terms of predictive ability.The primary objectives of this thesis are (i) examining the predictive usefulness of semi-mechanistic models in T2DM by applying an existing population model to clinical data, and (ii) exploring the relationship between obesity and T2DM and describe it mathematically in a novel semi-mechanistic model to explain changes to the glucose-insulin homeostasis and disease progression of T2DM.Through the use of non-linear mixed effects modelling, the primary mechanism of action of an antidiabetic drug has been correctly identified using the integrated glucose-insulin model, reinforcing the predictive potential of semi-mechanistic models in T2DM. A novel semi-mechanistic model has been developed that incorporated a relationship between weight change and insulin sensitivity to describe glucose, insulin and glycated hemoglobin simultaneously in a clinical setting. This model was also successfully adapted in a pre-clinical setting and was able to describe the pathogenesis of T2DM in rats, transitioning from healthy to severely diabetic.This work has shown that a previously unutilized biomarker was found to be significant in affecting glucose homeostasis and disease progression in T2DM, and that pharmacometric models accounting for the effects of obesity in T2DM would offer a more complete physiological understanding of the disease.
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| 2. |
- Nilsson, Anders K., 1982, et al.
(författare)
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PSB33 protein sustains photosystem II in plant chloroplasts under UV-A light
- 2020
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Ingår i: Journal of Experimental Botany. - OXFORD ENGLAND : Oxford University Press (OUP). - 0022-0957 .- 1460-2431. ; 71:22, s. 7210-7223
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Tidskriftsartikel (refereegranskat)abstract
- Plants can quickly and dynamically respond to spectral and intensity variations of the incident light. These responses include activation of developmental processes, morphological changes, and photosynthetic acclimation that ensure optimal energy conversion and minimal photoinhibition. Plant adaptation and acclimation to environmental changes have been extensively studied, but many details surrounding these processes remain elusive. The photosystem II (PSII)-associated protein PSB33 plays a fundamental role in sustaining PSII as well as in the regulation of the light antenna in fluctuating light. We investigated how PSB33 knock-out Arabidopsis plants perform under different light qualities. psb33 plants displayed a reduction of 88% of total fresh weight compared to wild type plants when cultivated at the boundary of UV-A and blue light. The sensitivity towards UV-A light was associated with a lower abundance of PSII proteins, which reduces psb33 plants' capacity for photosynthesis. The UV-A phenotype was found to be linked to altered phytohormone status and changed thylakoid ultrastructure. Our results collectively show that PSB33 is involved in a UV-A light-mediated mechanism to maintain a functional PSII pool in the chloroplast.
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