Data from: Modelling of dysregulated glucagon secretion in type 2 diabetes by considering mitochondrial alterations in pancreatic alpha cells

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 hypoglycemia 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.