Human alpha and gamma pancreatic cells can be reprogrammed to produce insulin, reports a paper published online this week in Nature. Typically, only pancreatic beta cells produce insulin. The modified cells can also relieve the symptoms of diabetes when transplanted into diabetic mice.
The conversion of cells into different cell types when stressed is a widespread regenerative strategy in animals but is poorly documented in mammals. In mice, pancreatic non-beta cells can produce insulin if insulin-secreting islet beta cells are destroyed. It is unknown whether human pancreatic cells can display the same plasticity.
Pedro Herrera and colleagues investigated whether human pancreatic alpha and gamma cells from diabetic and non-diabetic donors could be reprogrammed to produce insulin in response to glucose. The authors report that increased expression of two key transcription factors (Pdx1 and MafA) enabled cells to produce insulin - the first direct evidence of plasticity of mature human non-beta pancreatic cells.
The authors then tested whether these insulin-producing human alpha cells could relieve the clinical signs of type 1 diabetes in mice that lack insulin-secreting beta cells. When insulin-producing alpha cells from multiple donors were transplanted, glucose tolerance, secretion, and blood levels were all normalized in the mice. The cells continued to secrete insulin for up to six months after transplantation.
These findings provide conceptual evidence for plasticity of human pancreatic cells. Fostering this plasticity to replace missing cell populations could represent a potential treatment for diabetes and other degenerative diseases.