The effects of mitochondrial physical properties on insulin secretion in mouse pancreatic beta cell (β-cell) line MIN6

March Meeting 2024 Abstract

PI: Shankar Mukherji, Washington University in St. Louis



Diabetes mellitus refers to a group of diseases that impact how your body converts sugar into cellular energy in the form of ATP. Research on diabetes has focused on the biochemical pathway that allows cells to secrete insulin granules in response to sugar, with the role mitochondria (e.g. mtDNA) have in this pathway. In this work, we focus on cellular-level biophysical properties, and create a model for how mitochondrial number, size, and physical distribution in space impact how a cell can secrete insulin in response to varying glucose concentrations. We use MIN6, a cell line derived from a mouse pancreas, as our model system, and analyze the cell’s varying responses across a titration of glucose conditions (2mM-22mM); in addition, we analyze how the mitochondrial network redistributes upon addition of cytoskeleton inhibitors/enhancers- nocodazole and somatostatin. We find a positive correlation between mitochondrial volume fraction and insulin secretion. In addition, we come across data that indicates a spatial redistribution for mitochondria, with cell stressors leading to more peripheral mitochondrial. This network reshaping better positions the mitochondria to respond to diffusion-limited processes in beta-cells, such as response to changes in glucose concentration, and secretion of insulin granules.