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This article originally posted 13 April, 2010 and appeared in

Issue 517

Cells in Pancreas Can Spontaneously Change into Insulin-Producing Cells

Alpha cells in the pancreas, which do not produce insulin, can convert into

insulin-producing beta cells, advancing the prospect of regenerating beta

cells

as a cure for Type 1 diabetes....

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Researchers at the University of Geneva, led by Dr. Pedro L. Herrera,

demonstrated that beta cells will spontaneously regenerate after near-total

beta cell

destruction in mice and the majority of the regenerated beta cells are

derived from alpha cells that had been reprogrammed, or converted, into beta

cells.

Using a unique model of diabetes in mice, in which nearly all of the beta

cells are rapidly destroyed, the researchers found that if the mice were

maintained

on insulin therapy, beta cells were slowly and spontaneously restored,

eventually eliminating the need for insulin replacement. Alpha cells

normally reside

alongside beta cells in the pancreas and secrete a hormone called glucagon,

which works opposite to insulin to regulate the levels of sugar in the

blood.

Alpha cells are not attacked by the autoimmune processes that destroy beta

cells and cause Type 1 diabetes.

Type 1 diabetes is a chronic, autoimmune disease that affects children,

adolescents and adults, in which the immune system attacks the beta cells in

the

pancreas that produce insulin, a hormone that enables people to convert food

into energy. People with Type 1 diabetes are dependent on insulin treatment

for the rest of their life.

Dr. Herrera's results are the first to show that beta cell reprogramming can

occur spontaneously, without genetic alterations. Previous efforts to

reprogram

non-beta cells into beta cells relied on genetic manipulations -- processes

that can not be easily translated into therapies.

According to Dr. Rakeman, JDRF Program Manager in Beta Cell

Therapies, the breakthrough in Dr. Herrera's work is the demonstration that

alpha- to-beta-cell

reprogramming can be a natural, spontaneous process. " 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, " he

said. " It appears that the body can restore beta cell function either

through

reprogramming alpha cells to become beta cells or, as previously shown by

others, by increasing growth of existing beta 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 beta cells. "

Dr. Herrera's team genetically engineered the animals to be susceptible to a

toxin that would destroy only their beta cells. When the mice were exposed

to the toxin, the beta cells were rapidly and efficiently destroyed --

greater than 99% just 15 days after treatment. Then, to track the source of

newly

regenerated beta cells, Dr. Herrera's team used another genetic manipulation

to permanently label mature alpha cells and all their descendents with a

fluorescent

protein. This " genetic lineage tracing " approach allowed the scientists to

track the fate of the alpha cells and their progeny; the presence of

fluorescently

labeled beta cells in the recovered animals gave conclusive evidence that

alpha cells had reprogrammed into beta cells.

The Geneva researchers pointed out that the critical factor in sparking the

alpha-to- beta-cell reprogramming was removing (or ablating) nearly all the

original insulin-producing cells in the mice. In mice where the loss of

beta cells was more modest, the researchers either found no evidence of beta

cell

regeneration (when only half the cells were destroyed) or less alpha cell

reprogramming (when less than 95% of cells were destroyed).

" The amount of beta-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 Dr. Herrera.

In Type 1 diabetes, the immune system attacks beta cells, stopping a

person's pancreas from producing insulin, the hormone that enables people to

get energy

from sugar. Beta cell regeneration involves triggering the body to grow its

own new insulin producing cells, either by copying existing ones -- some are

usually still active, even in people who have had diabetes for decades -- or

causing the pancreas to create new ones.

In addition to regenerating or replacing insulin producing cells, a cure for

Type 1 diabetes will also require stopping the autoimmune attack that causes

diabetes, and reestablishing excellent glucose control.

Nature April, 2010

Amylin, Lilly's Byetta May Have Cancer Risk, FDA Says

One out of every 10 healthcare dollars is spent

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This article originally posted 13 April, 2010 and appeared in

Issue 517

Past five issues:

Issue 517 |

Issue 516 |

Issue 515 |

Issue 514 |

Issue 513 |

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