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Israeli medical researchers unexpectedly discovered that only when a baby is weaned off mother’s milk does a formerly unknown developmental step in the process of pancreatic beta-cell maturation begin to occur.

In experiments with lab mice, this critical developmental step appeared to be triggered exclusively by the change of diet.

The surprising discovery was made while scientists were attempting to understand why only a small subset of insulin-producing beta cells in the pancreas of adult organisms can replicate – leading to tissue regeneration – and why the number of replicating cells declines with advancing age.

The study results were published in the March 9 issue of the medical journal Developmental Cell by Prof. Yuval Dor and research associate Miri Stolovich-Rain at the Hebrew University of Jerusalem’s Institute for Medical Research Israel-Canada, in collaboration with Prof. Benjamin Glaser from the Hadassah Medical Center in Jerusalem.

Hoping to understand the effects of aging on beta-cell replication, the scientists induced hyperglycemia – a condition of excessive glucose (sugar) in the bloodstream – in suckling mice, expecting that because of their young age their beta cells would exhibit a superb regenerative ability.

Instead, the researchers discovered that the mice actually didn’t begin to develop the cellular machinery that allows for tissue regeneration until after they were weaned from high-fat mother’s milk (or formula) to high-carbohydrate chow.

In addition, insulin secretion in response to high levels of glucose was much lower in the suckling mice than in adult mice.

Prof. Yuval Dor
Prof. Yuval Dor

“The data suggest that regenerative potential is a trait of mature tissues, which has to develop actively, similar to functional maturation, rather than an innate feature of newly born cells,” said Dor, a developmental biologist.

When to wean

The researchers concluded that the dietary transition from fat-rich milk to carbohydrate-rich food kick-starts the maturation of beta cells so that they can replicate and secrete proper amounts of insulin in response to conditions such as high blood-glucose levels.

The exact molecular signal that sets off these events is still to be determined through further research that could help advance the understanding of diabetes and even how to treat it.

It’s possible, for instance, that the maturation step associated with weaning can be relevant for attempting to direct the differentiation of embryonic stem cells into fully functional beta cells for transplantation to diabetes patients.

Next, the Israeli researchers plan to study how premature weaning in mice and in humans may affect the long-term health of beta cells and the chances of developing diabetes .

Dor is careful to stress that the published findings should not make mothers fretful about weaning their babies from breast milk or formula too early or too late.

“We are NOT saying in this paper anything about the long-term effects, good or bad, of premature weaning,” he wrote to ISRAEL21c in an email. “What we found is that weaning triggers beta-cell maturation and that it is a previously unrecognized part of this important process.The long-term impact of interfering with the process by premature or delayed weaning is being studied now.”

The research was funded by grants from the Beta Cell Biology Consortium of the US National Institutes of Health, the JDRF, the European Research Council, the Helmsley Charitable Trust, the DON Foundation, BIRAX and the I-CORE Program of the Israel Science Foundation.

Previously, Dor and James Shapiro, a world renowned researcher in islet transplantation for diabetes at the University of Alberta, Canada, identified a key signal that prompts insulin-producing beta cells in the pancreas to form new beta cells in mice. This breakthrough may ultimately help researchers find ways to restore or increase beta cell function in people with type 1 diabetes.