Up until puberty, the pancreas is more adaptable and possesses a greater potential for self-healing than had previously been assumed. This is the conclusion reached by a study with mice funded through the National Research Programme "Stem Cells and Regenerative Medicine" (NRP 63).
Approximately 40,000 persons in Switzerland suffer from type-1 diabetes. The illness is caused by the loss of so-called pancreatic beta cells, the cells that produce the hormone insulin, which is essential for regulating the use of sugar in the body. Since beta cells do not regenerate, scientists have traditionally assumed that the loss of these cells is irreversible; indeed, diabetic patients require insulin injections for life.
Previously unknown mechanism
Four years ago, the research team of Pedro Herrera (University of Geneva) first cast doubt on this assumption when they demonstrated that a few alpha cells in the pancreas of genetically modified diabetic mice changed into beta cells. Alpha cells normally produce the blood sugar-raising hormone glucagon, but in diabetic mice they started producing insulin instead. Herrera's team has now made a second discovery, which has just been published in the journal Nature: in prepubescent mice the pancreas is capable of compensating the loss of insulin-producing beta cells. "This is achieved by a mechanism unknown until now," says Herrera. The process involves the reversion of delta cells (which produce somatostatin, another pancreatic hormone) to a precursor-like cell state, with proliferation and later reconstitution of the populations of beta and delta cells.
In contrast to the conversion of alpha cells, which only concerns a small fraction of the alpha cell population, the new mechanism involving delta cell fate change is a more efficient way of offsetting the loss of beta cells and thus diabetes recovery. Yet while alpha cells can reprogram into insulin production also in old mice, the ability of delta cells to do so is limited and does not extend beyond puberty.
Human pancreas can regenerate too
Although Herrera's group has investigated the versatility of pancreatic cells in mice, several observations in diabetic patients suggest that the human pancreas is capable of transformation too. "The new mechanism shows that the pancreas is much more plastic and -- at least during childhood -- possesses a much greater potential for self-healing than we had previously assumed," says Herrera. "There is still a long way to go before diabetes patients might be able to benefit from these findings, but the discovery that delta cells have a high degree of plasticity points to a hitherto unsuspected option for therapeutic intervention."
- Simona Chera, Delphine Baronnier, Luiza Ghila, Valentina Cigliola, Jan N. Jensen, Guoqiang Gu, Kenichiro Furuyama, Fabrizio Thorel, Fiona M. Gribble, Frank Reimann, Pedro L. Herrera. Diabetes recovery by age-dependent conversion of pancreatic δ-cells into insulin producers. Nature, 2014; DOI: 10.1038/nature13633
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