What if newborns and infants could help us advance diabetes nanomedicine?


"Collect in your youth, you will find in your old age".

In this popular Berber saying, several messages can be heard. One of them is the importance of the health capital of youth for "aging well". In reality, this health capital is amassed from the time of the newborn and the infant. If blood sugar is finely regulated and we do not develop diabetes, it is thanks to the amazing capacity of the insulin-secreting cells, called pancreatic beta cells, to adapt its cell mass and the quantity of insulin produced during changes in eating habits or during a pregnancy, for example. In fact, this tremendous plasticity, expressed in the form of a partition or epigenetic code, is created during the feeding periods of newborns and infants. This same code is found in the performing cells of overweight or obese individuals who do not develop diabetes.

All cells in our body have the same DNA. If we were to compare a cell to a computer, this DNA would be the "hardware". In fact, all cells also have the same genes. However, the genes are not expressed in the same way in all cells. This is what determines the identity of a cell and, consequently, what characterizes the organs between them. This character of a cell is determined by its genetics and by its epigenetics. Epigenetics refers to the hundreds or even thousands of biochemical modifications that a cell's DNA and the proteins that surround it undergo in response to its environment. In fact, these epigenetic modifications constitute a kind of software that programs and above all adapts the functioning of a cell to its environment. Cells specialize in their environment thanks to epigenetics.

Beta cells have the exclusive right to produce insulin, 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 volume and number when body mass increases and when overeating rich in fats and carbohydrates is chronic. 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 becomes active again in adult beta cells, when we are confronted with weight gain, pregnancy or excessive feeding, in order to increase cell mass and insulin production...

In diabetic patients, some of the epigenetic modifications that make up this software are altered, suggesting that a breakdown in the software may be responsible for the inability of beta cells to adapt their mass and insulin production to chronic hyperglycemia. Newborns of diabetic parents also have a higher risk of developing diabetes, suggesting that this failure is passed on to offspring. Let's not forget that diabetes is a scourge, 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 allow to find new drug targets, whose delivery and transport in the blood could 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