New hope for diabetics

Targeted inhibitor protein suppression accelerates beta cell division

NanoNewsNet based on the materials of PennMedicine: Silencing Inhibitor of Cell Replication Spurs Insulin-producing Beta Cells to ReproduceScientists from the Perelman School of Medicine of the University of Pennsylvania (Perelman School of Medicine, University of Pennsylvania) and the Hadassah Medical Center of the Hebrew University (Hadassah-Hebrew University Medical Center) managed to accelerate the reproduction of beta cells of the human pancreas, which produce the hormone insulin vital for the body, by transplanting donor cells into the body of mice.

But first they suppressed the activity of one of the proteins in them. The new cells retain the characteristic features of mature beta cells and demonstrate a physiological response to glucose.

The researchers published their study in The Journal of Clinical Investigation (Avrahami et al., Targeting the cell cycle inhibitor p57Kip2 promotes adult human beta cell replication).

The results of this experiment, which provided evidence of the validity of this concept, are relevant for the treatment of patients with both type 1 and type 2 diabetes. In type 1 diabetes, beta cells are destroyed by the patient's own immune system, and, therefore, restoring their number should be combined with preventing their destruction by the immune system. Similarly, a decrease in the number of functional insulin-producing beta cells contributes to the development of type 2 diabetes. Thus, restoring the mass of beta cells can improve the condition of patients with both forms of diabetes.

This study was inspired by an "experiment" set up by nature itself – a well-known, albeit rare condition called hyperinsulinism of newborns, in which the pancreas produces too much insulin (the exact opposite of diabetes). Blood sugar levels in infants born with this disease are very low. In about a third of them, most beta cells are healthy, but a small part of the cells lack the specific protein p57, which is explained by a mutation that occurred in one or more beta cells during intrauterine development. Protein p57 is an inhibitor of the cell cycle, and its absence accelerates the reproduction of beta cells. As a result, a large cell clone is created in the pancreas, secreting too much insulin.

Using short hairpin RNA (shRNA), the researchers suppressed the p57 gene in human beta cells obtained from deceased adult donors and transplanted these cells into mice with a diabetes model.

After three weeks, the rate of beta cell replication in the graft was at least three times higher than in control grafts without p57 suppression. The new beta cells produced proteins characteristic of normal mature human beta cells – insulin, PDX1 and NKX6 1.

In beta cells with suppressed p57, DNA can replicate.
Pink shows the nucleus that has undergone DNA replication, green
– insulin, blue – DNA–stained nuclei, white - p57.
(Photo: Klaus Kaestner, PhD, Perelman School of Medicine, University of Pennsylvania; JCI)

These data show that normally non-replicating beta cells, obtained even from old donors, can be forced to divide while preserving the properties of mature beta cells, which many scientists previously considered almost impossible.

The authors of the study believe that in 10-15 years doctors will be able to treat patients with diabetes mellitus using a means that specifically delivers a molecule that suppresses p57 to beta cells. This will increase the number of beta cells, increase the synthesis of insulin and, perhaps, even completely cure the disease.

Portal "Eternal youth" http://vechnayamolodost.ru21.01.2014