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- Grubelnik, V, et al.
(författare)
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Modelling of dysregulated glucagon secretion in type 2 diabetes by considering mitochondrial alterations in pancreatic α-cells
- 2020
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Ingår i: Royal Society open science. - : The Royal Society. - 2054-5703. ; 7:1, s. 191171-
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes mellitus (T2DM) has been associated with insulin resistance and the failure of β-cells to produce and secrete enough insulin as the disease progresses. However, clinical treatments based solely on insulin secretion and action have had limited success. The focus is therefore shifting towards α-cells, in particular to the dysregulated secretion of glucagon. Our qualitative electron-microscopy-based observations gave an indication that mitochondria in α-cells are altered in Western-diet-induced T2DM. In particular, α-cells extracted from mouse pancreatic tissue showed a lower density of mitochondria, a less expressed matrix and a lower number of cristae. These deformities in mitochondrial ultrastructure imply a decreased efficiency in mitochondrial ATP production, which prompted us to theoretically explore and clarify one of the most challenging problems associated with T2DM, namely the lack of glucagon secretion in hypoglycaemia and its oversecretion at high blood glucose concentrations. To this purpose, we constructed a novel computational model that links α-cell metabolism with their electrical activity and glucagon secretion. Our results show that defective mitochondrial metabolism in α-cells can account for dysregulated glucagon secretion in T2DM, thus improving our understanding of T2DM pathophysiology and indicating possibilities for new clinical treatments.
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- Rodriguez, A, et al.
(författare)
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Fitness, Food, and Biomarkers: Characterizing Body Composition in 19,634 Early Adolescents
- 2022
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- Adolescent obesity persists as a major concern, especially in Central and Eastern Europe, yet evidence gaps exist regarding the pivotal early adolescent years. Our objective was to provide a comprehensive picture using a holistic approach of measured anthropometry in early adolescence, including body composition, cardiorespiratory fitness (CRF), and reported lifestyle characteristics. We aimed to elucidate potential sex/gender differences throughout and associations to biomarkers of disease risk for obese adolescents. Methods: Trained nurses measured 19,634 early adolescents (12–14-year-olds), we collected parental reports, and, for obese adolescents, fasting blood samples in four major Polish cities using a cross-sectional developmental design. Results: 24.7% boys and 18.6% girls were overweight/obese, and 2886 had BMI ≥ 90th percentile. With increasing age, there was greater risk of obesity among boys (p for trend = 0.001) and a decreasing risk of thinness for girls (p for trend = 0.01). Contrary to debate, we found BMI (continuous) was a useful indicator of measured fat mass (FM). There were 38.6% with CRF in the range of poor/very poor and was accounted for primarily by FM in boys, rather than BMI, and systolic blood pressure in girls. Boys, in comparison to girls, engaged more in sports (t = 127.26, p < 0.0001) and consumed more fast food (t = 188.57, p < 0.0001) and sugar-sweetened beverages (167.46, p < 0.0001). Uric acid, a potential marker for prediabetes, was strongly related to BMI in the obese subsample for both boys and girls. Obese girls showed signs of undernutrition. Conclusion: these findings show that overweight/obesity is by far a larger public health problem than thinness in early adolescence and is characterized differentially by sex/gender. Moreover, poor CRF in this age, which may contribute to life course obesity and disease, highlights the need for integrated and personalized intervention strategies taking sex/gender into account.
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