Systems Biology Theory Clarification of a Controversy in Pancreatic Beta Cell Regeneration

Abstract

27Whether new pancreatic beta-cells arise via pre-existing beta-cells or from 28 differentiation of precursor cells -a question of fundamental importance for diabetic 29 therapy -has long been debated. Recent experiments suggest that multipotent 30 precursors from adult mouse pancreas, that give rise to beta-cells, do exist. However, 31 such a finding is at odds with prior evidence that beta-cell expansions occurs 32 exclusively through self-replication. Here we show that these two observations can be 33 partially compatible. We use a systems biology approach to analyze the dynamics of 34 the endogenous molecular-cellular network in the pancreas. Our results show that self-35 replicating 'beta-cells' can themselves be multipotent precursors. In addition, our model 36 predicts heterogeneity in beta-cell regeneration and suggests various differentiation 37 paths of precursors. This work therefore provides a means of reconciling an apparent 38 contradiction in the field, but also sheds light on possible paths of beta-cell regeneration 39 from a systems biology perspective. 40 41

Regeneration of Pancreatic Beta Cells by Modulation of Molecular Targets Using Plant-Derived Compounds: Pharmacological Mechanisms and Clinical Potential

“…Consequently, despite treatment, in the majority of the patients, T2D deteriorates progressively over time, eventually necessitating insulin supplementation [ 6 , 7 , 8 ]. This progressive clinical deterioration of T2D has inspired the search for new therapeutics that arrest the disease’s progression, protect the remaining pancreatic beta cells, and restore beta-cell mass in T2D by exploiting the inherent plasticity of the pancreas [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”