Diabetes enhances the proliferation of adult pancreatic multipotent progenitor cells and biases their differentiation to more β-cell production.
Endogenous pancreatic multipotent progenitors (PMPs) are ideal candidates for regenerative approaches to compensate for β-cell loss since their β-cell-producing capacities as well as strategic location would eliminate unnecessary invasive manipulations. However, little is known about the status and potentials of PMPs under diabetic conditions. Here we show that β-cell metabolic stress and hyperglycemia enhance the proliferation capacities of adult PMP cells and bias their production of progeny toward β-cells in mouse and human. These effects are dynamic and correlate with functional β-cell regeneration when conditions allow.
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada rozy.razavi@gmail.com.
Rozita
R
Razavi
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
Hamed S
HS
Najafabadi
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Sarah
S
Abdullah
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Simon
S
Smukler
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Margot
M
Arntfield
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Derek
D
van der Kooy
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology*