Ability of pancreatic cells to change type gives hope for diabetes therapy
MedWire News: Results from a study in mice show that glucagon producing pancreatic α-cells are able to regenerate as insulin-producing β-cells in conditions of extreme β-cell loss, which researchers hope may help in the development of therapies for patients with diabetes.
“If we can understand the signals that are triggering this conversion, it will open a whole new potential strategy for regenerating beta cells in people with Type 1 diabetes,” commented Andrew Rakeman (Juvenile Diabetes Research Foundation International, USA).
He added: “It appears that the body can restore β-cell function either through reprogramming α-cells to become β-cells or, as previously shown by others, by increasing growth of existing β -cells. This path may be particularly useful in individuals who have had the disease for a long time and have no, or very few, remaining β-cells.”
Fabrizio Thorel (University of Geneva, Switzerland) and colleagues created a transgenic mouse model of diphtheria-toxin-induced acute selective near-total β-cell ablation to assess the ability of adult mice to regenerate new β-cells after total β-cell loss, such as that seen in advanced Type 1 diabetes.
The researchers found that if the mice were given insulin they survived and began to regenerate new β-cells over time.
The team labeled the pancreatic α-cells of the mice before β-cell loss took place. This allowed them to observe that a large fraction of the new β-cells were derived from α-cells, showing a previously overlooked degree of pancreatic cell plasticity.
The key factor influencing the cell reprogramming appeared to be the removal or destruction of the majority of β-cells. When only half the β-cells were destroyed no significant evidence of β-cell regeneration was seen. When less than 95% of the β-cells were destroyed regeneration occurred, but α- to β-cell conversion was minimal.
“The amount of β-cell destruction thus appears to determine whether regeneration occurs. Moreover, it influences the degree of cell plasticity and regenerative resources of the pancreas in adult organisms,” said study co-author Pedro Herrera (University of Geneva, Switzerland).
Writing in the journal Nature, the authors conclude: “Such inter-endocrine spontaneous adult cell conversion could be harnessed towards methods of producing β-cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration.”
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By Helen Albert