Determinants of pancreatic beta-cell regeneration.
Recent studies have revealed a surprising plasticity of pancreatic beta-cell mass. beta-cell mass is now recognized to increase and decrease in response to physiological demand, for example during pregnancy and in insulin-resistant states. Moreover, we and others have shown that mice recover spontaneously from diabetes induced by killing of 70-80% of beta-cells, by beta-cell regeneration. The major cellular source for new beta-cells following specific ablation, as well as during normal homeostatic maintenance of adult beta-cells, is proliferation of differentiated beta-cells. More recently, it was shown that one form of severe pancreatic injury, ligation of the main pancreatic duct, activates a population of embryonic-type endocrine progenitor cells, which can differentiate into new beta-cells. The molecular triggers for enhanced beta-cell proliferation during recovery from diabetes and for activation of embryonic-type endocrine progenitors remain unknown and represent key challenges for future research. Taken together, recent data suggest that regenerative therapy for diabetes may be a realistic goal.
Department of Cellular Biochemistry and Human Genetics, The Institute of Medical Research, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
A
A
Khalaileh
T
T
Gonen-Gross
J
J
Magenheim
T
T
Nir
S
S
Porat
S
S
Salpeter
M
M
Stolovich-Rain
A
A
Swisa
N
N
Weinberg
Y
Y
Dor
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D003920:Diabetes Mellitus / Q000503:physiopathology*; D005260:Female; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*