What if newborns and infants could help us to make the progress in diabetes nanomedicine?

« Gather in your youth, you will find in your old age ».

In this popular Berber saying, several take-home messages can be heard. One of them is the importance of the health capital of youth for the «well-aging ». In reality, this health capital is amassed during the newborn and the infant periods. We do not develop diabetes thanks to the amazing capacity of the insulin-secreting cells, called pancreatic beta-cells, to adapt their mass and the quantity of insulin to some changes in eating habits or during a pregnancy, for example. In fact, this tremendous plasticity of beta-cells results from a kind a partition or epigenetic code, which is established during the breastfeeding periods of newborns and infants. The same epigenetic code is found in the highly adaptive of “super beta-cells” of overweight or obese individuals who do not develop diabetes.

In our body, all cells have the same DNA. If we compare a cell to a computer, the DNA would be the « hardware ». Therefore, all cells also have the same genes. However, the genes are not expressed and not regulated at the same level in cells. In fact, the gene differential expression makes the identity of a cell and, consequently, determines the type and specificity of organs. The cell character is determined by its genetics and by its epigenetics. Epigenetics refers to the hundreds or even thousands of biochemical modifications that target cell’s DNA and the proteins that surround it in response to its environment. These epigenetic modifications constitute a kind of software that programs and adapts the cell function to its environment. In other words, epigenetic makes the cells living and expert to its environment..

Beta cells have the exclusivity to produce insulin, which is the only hormone that reduces blood sugar in the body. They secrete a significant amount of this hormone into the bloodstream when blood sugar levels rise. Architecturally, beta cells are also very plastic. They are able to increase in their volume and number when body mass increases and when our we have bad dietary habits such eating too much for long fats and carbohydrates. This plasticity and the ability of cells to secrete insulin in response to glucose are established by a software set up between the period of exclusive breastfeeding of the newborn and the period of weaning, characterized by the appearance of a diet rich in sugar. Once the diet is acquired, this software becomes silent in adulthood. However, a body of evidence supports the hypothesis that this software is reactivated in adult beta cells, during weight gain, pregnancy or excessive feeding, in order to increase cell mass and insulin production…

In patients with diabetes, some of the epigenetic modifications of this software are altered, suggesting that the software alteration is responsible for the inability of beta cells to adapt their mass and insulin production to chronic hyperglycemia. Newborns from parents with diabetes have a higher risk of developing diabetes, suggesting that the software failure is transmitted to offspring. We cannot forget that diabetes is one of the deadliest diseases, which kills several million people in the world every year, and that it reduces on average 6 years of life expectancy to the patient.
Some defective sequences of the software have been identified, but much remains to be discovered. Their identification will enable to find new drug targets, whose delivery and transport in the blood can be optimized thanks to nanotechnologies, one of the research axes undertaken by the NBI team…

2022-jun | Trends in endocrinology and metabolism: TEM 33 (6) , pp.378-389