Ny avhandling om insulinsignalering i betacellen i genetiska och diet modeller av fetma och insulinresistens
Meike Paschen vid forskargruppen Signaltransduction försvarar sin avhandling "Pancreatic βeta-cell insulin signaling in genetic and dietary models of obesity and insulin resistance" den 22 mars, 2019. Huvudhandledare är Ingo Leibiger.
What's the main focus of your thesis?
My thesis focuses on insulin resistance in the pancreatic β-cell that is part of the islet of Langerhans which is located in the pancreas.
Which are the most important results?
The results show that β-cell insulin resistance can be monitored longitudinally and non-invasively in vivo employing the in vivo imaging platform and a by us constructed β-cell insulin resistance biosensor (βIRB). Islets that are transduced with βIRB were transplanted to the anterior chamber of the eye of mice and monitored over time in both genetic and diet-induced models of insulin resistance. The results demonstrated that β-cell insulin resistance goes along with whole body insulin resistance, impaired glucose tolerance and increased bodyweight. In general β-cell insulin resistance dynamics are different in different models of insulin resistance. Furthermore the results show for the first time that β-cell insulin resistance is relevant in the context of diet-induced insulin resistance and was seen when C57BL/6J (B6) mice are fed a High-Fat-High-Sucrose-Diet (HFHSD). β-cell insulin resistance in B6 mice fed a HFHSD is accompanied by decreased functional β-cell mass and impaired insulin secretion due to a failure downstream of glucose-stimulated Ca2+ influx, in part due to a reduction of syntaxin-1A. β-cell insulin sensitivity and function can be restored by re-feeding of a normal diet.
How can this new knowledge contribute to the improvement of people's health?
Demonstrating how fast β-cell insulin resistance can develop when a diet rich in fat and sugar is consumed and that it is possible to improve β-cell function by following a healthy diet underlines the importance of a healthy life style and its direct contribution to improved health.
What are your future ambitions?
A healthy life style is (most often) a very simple and cheap treatment strategy both to avoid and to recover from (pre-)diabetes, however many people have difficulties to live a healthy life. I would like to contribute to make a healthy life easier for many people, thus contributing to a healthier society.