Mathematical modeling clarifies the paracrine roles of insulin and glucagon on the glucose-stimulated hormonal secretion of pancreatic alpha- and beta-cells

Introduction Blood sugar homeostasis relies largely on the action of pancreatic islet hormones, particularly insulin and glucagon. In a prototypical fashion, glucagon is released upon hypoglycemia to elevate glucose by acting liver while elevated induces secretion which leads uptake peripheral tissues. This simplified view does not consider paracrine roles two hormones modulating response α- β-cells. particular, glucose-stimulated isolated α-cells exhibits Hill-function pattern, experiments with intact islets suggest ‘U’-shaped response. Methods To this end, framework was developed based first principles coupled experimental studies capturing glucose-induced β-cells influenced hormones. The model predicts both transient steady-state profiles secreted glucagon, including typical biphasic normal hyperglycemia. Results discussion results underscore activity as differentiating factor from whole vs . α-cells, highlight importance conditions in interpreting behavior cells vitro also reproduces hyperglucagonemia, experienced diabetes patients, it linked failure inhibit α-cell activity. described here amenable inclusion additional cell types extrapancreatic tissue simulating multi-organ systems. study expands our understanding interplay for pancreas function pathological conditions.