Publications by authors named "S E Millership"
Article Synopsis
- GLP-1 receptor agonists are effective for treating type 2 diabetes and obesity, but patient responses vary due to genetic differences.
- A specific genetic variant (A316T) shows protective effects against T2D and cardiovascular disease and leads to improved blood glucose and insulin levels in a mouse model.
- However, this variant results in reduced effectiveness when using GLP-1R agonist medications, highlighting the need to understand genetic variations for personalized treatment strategies.
Aims/hypothesis: Beta cells within the pancreatic islet represent a heterogenous population wherein individual sub-groups of cells make distinct contributions to the overall control of insulin secretion. These include a subpopulation of highly connected 'hub' cells, important for the propagation of intercellular Ca waves. Functional subpopulations have also been demonstrated in human beta cells, with an altered subtype distribution apparent in type 2 diabetes.
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- The study explores the heterogeneous nature of beta cells in the pancreatic islet, highlighting how different subpopulations contribute uniquely to insulin secretion, especially in the context of type 2 diabetes.
- It examines the role of the imprinted gene neuronatin (NNAT) in insulin synthesis and its expression patterns in both mice and human beta cells, suggesting that epigenetic changes may influence beta cell function.
- Utilizing advanced techniques like single-cell RNA sequencing and proteomics, the research indicates that distinct beta cell populations emerge during embryonic development, regulated by DNA methylation processes.
Transmission of epigenetic information between generations occurs in nematodes, flies and plants, mediated by specialised small RNA pathways, modified histones and DNA methylation. Similar processes in mammals can also affect phenotype through intergenerational or trans-generational mechanisms. Here we generate a luciferase knock-in reporter mouse for the imprinted Dlk1 locus to visualise and track epigenetic fidelity across generations.
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- Synucleins are a family of proteins, with α-synuclein being primarily linked to Parkinson's disease, but the roles of other family members like β-synuclein and γ-synuclein in neurotransmission are less understood.
- This study found that mice lacking β-synuclein showed decreased dopamine uptake in synaptic vesicles, while reintroducing β-synuclein improved this function, unlike α-synuclein or γ-synuclein.
- The findings suggest that β-synuclein may enhance dopamine uptake by altering the protein structure of synaptic vesicles, potentially protecting dopaminergic neurons from toxic effects associated with Parkinson's disease.