Image credit: Leibowitz et al. 2018 (CC BY 4.0)
Insulin is a hormone that is crucial for maintaining normal blood sugar levels and is produced by so called β-cells in the pancreas. If the body stops making insulin, or cells stop responding to it, blood sugar levels rise, leading to diabetes. A form of diabetes known as type 1 diabetes, where the body stops making insulin, usually starts in childhood and can sometimes appear during the first six months of life.
Infants affected by this early onset of diabetes have mutations in one copy of the gene that encodes insulin. They can still produce half of the amount of insulin, which should be sufficient to control blood sugar to a certain extent. Instead, insulin production stops almost completely after a few months. Scientists believe that this is because the mutant insulin has a toxic effect on β-cells.
Mutations in the insulin gene affect the structure of insulin. As a result, insulin builds up in the β-cells, which may eventually cause the cells to die. But the mutant insulin might also cause a problem with a molecule called mTORC1, which helps β-cells to grow.
To investigate this further, Riahi et al. used a mouse model of this form of diabetes to study how stress affects β-cells from birth to adulthood. Mutant β-cells slowed down their rate of cell growth and division early after birth, but did not die more frequently. The results also revealed that β-cells had lower levels of mTORC1, which probably is the main cause of the reduced cell division and growth. When mTORC1 levels were boosted experimentally, the β-cells started to grow and produce more insulin.
Understanding β-cell biology and the link between stress and growth, especially early in life, is a key step in understanding diabetes. In a separate study, Balboa et al. found that human β-cells with insulin mutations also had low mTORC1 and struggled to grow. If boosting mTORC1 could rescue β-cell growth in humans, it could lead to new ways to prevent diabetes.
