Islets of youth  pg. 3

Christopher V.E. Wright, D.Phil., who directs the Vanderbilt Program in Developmental Biology, agrees.

“What is the nature of the autoimmune problem in diabetes?” he asks. Is the immune system of these patients dysfunctional, such that it mistakes normal tissue for a germ and attacks it? Or could the beta cell be displaying the wrong “badge” on its surface, one that attracts “friendly fire?”

One way to answer these questions is to figure out the steps that lead to the development of the beta cell, and then to try to determine whether that differentiation program is “messed up” in the patient with diabetes.

That’s where the embryo may help.

During a part of embryonic development called gastrulation, groups of cells migrate into three distinct layers: the outer layer or ectoderm, which will develop into the nervous system and skin; a middle layer or mesoderm, which will become the musculature and other internal organs; and an inner layer, or endoderm, which will form the stomach, intestines, liver – and the pancreas.

The human pancreas secretes digestive enzymes and, from cells clustered in the islets of Langerhans, several important hormones, including insulin.

One of insulin’s main jobs is to ensure that fuel – primarily glucose – gets from the bloodstream into the tissues. Diabetes, characterized by a sustained and dangerous rise in blood levels of glucose, occurs when insulin production is unable to keep up with demand.

Whereas in type 1 diabetes there is a loss of beta cells, in type 2 diabetes, the most common form of the disease, the tissues of the body have become “resistant” to insulin. The beta cells also have lost their ability to produce sufficient levels of the hormone.

Wright believes developmental biology may hold the keys to unlocking the mystery of this ancient disorder.

“One of my strongest beliefs is that developmental biology and cancer biology and aging and all forms of inherited disease are basically the same process,” he says.

“Because the study of developmental biology involves trying to understand the generation of life, it uses and develops completely novel principles and tools and ways of looking at things to understand how multiple signaling pathways are used by cells to talk to each other in complicated ways.

“And because of that, it ends up being one of the most pioneering of disciplines.”

Pioneering discipline

Until the early 1980s, the mechanisms of development had been shrouded in mystery. Then, as the new tools of molecular biology became widely available, came several pivotal discoveries.

Among them: the discovery of the “homeobox,” from the Greek word for similar, a specific short sequence of DNA shared by a set of regulatory-switch genes in the fruit fly genome that determine which embryonic segments will become the future head, thorax and abdomen. Nearly identical sequences were found in the genes of vertebrates, including mice and humans.

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