Beta-cell mass and type 1 diabetes: going, going, gone?
OBJECTIVE
Beta-cell regeneration is a fundamental but elusive goal for type 1 diabetes research. Our objective is to review newer human and animal studies of beta-cell destruction and regeneration and consider the implications for treatment of type 1 diabetes.


METHODS
Recent human and animal studies of beta-cell destruction and regeneration in type 1 diabetes are reviewed.


RESULTS
The loss of beta-cells that characterizes type 1 diabetes reflects the net effects of destruction and regeneration. These processes have been examined in the nonobese diabetic (NOD) mouse; uncertainty remains about beta-cell dynamics in humans. Islet inflammation stimulates beta-cell replication that produces new insulin-positive cells. The regenerative process may tide the loss of overall beta-cell function, but it also may enhance the autoimmune attack on beta-cells by providing new epitopes. The highest rates of beta-cell replication are at the time of diagnosis of diabetes in NOD mice, and if autoimmunity and islet inflammation are arrested, new beta-cells are formed. However, the majority of beta-cells after treatment with immune modulators such as anti-CD3 monoclonal antibody, and most likely during the "honeymoon" in human disease, are recovered beta-cells that had been degranulated but present at the time of diagnosis of diabetes.


CONCLUSIONS
Residual beta-cells play a significant role for the design of therapeutic trials: they not only may respond to combination therapies that include stimulants of metabolic function but are also the potential source of new beta-cells.
Akirav
Eitan
E
Department of Immunobiology, Yale University, New Haven, Connecticut, USA.
Kushner
Jake A
JA
Herold
Kevan C
KC
D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D006801:Humans; D007167:Immunotherapy; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008954:Models, Biological