Multicellular regulation of the pancreatic islet in diabetes

Fine, Nicholas Hugh Francis ORCID: 0000-0003-2343-8534 (2023). Multicellular regulation of the pancreatic islet in diabetes. University of Birmingham. Ph.D.

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Abstract

Since the discovery of insulin-secreting beta cells and their role in glucose homeostasis, there has been an incredible focus on these cells and how they interact with other cells within the pancreatic islet to respond to increased blood glucose levels. This regulation requires both individual effort on the part of beta cells, as well as cooperative communication across the population. Until recently, all beta cells were considered equal, possessing a single programme of cell processes that enable them to function as required. In reality, there is a startling degree of variation within the beta cell population, and this variation, or heterogeneity, is required to maintain normoglycemia. For instance, some niche subpopulations of beta cells coordinate Ca2+ fluxes across the islet via gap junctions, while others possess the capacity to proliferate to restore beta cell numbers after an assault by immune or metabolic factors. Here, we aim to show that heterogeneity is vital for pancreatic function. We use a variety of cell and molecular techniques to interrogate functional changes in the islet after perturbating the islet’s normal heterogeneity by overexpressing beta cell identity genes or using exogenous steroids to alter gene expression.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):