The prevalence of diabetes in on the rise, and globally, 422 million people suffer from diabetes according to the latest (2016) WHO data. Diabetes encompasses a group of diseases characterized by either lack of the blood sugar-lowering hormone insulin, or inefficiency of the body to utilize this hormone. Clinical management of diabetes involves lifestyle modifications and blood sugar-lowering medications.
In a recent study, researchers at A*STAR Institute of Molecular and Cell Biology (IMCB) discovered a gene mutation that affects pancreatic development. The study found that mutation in the HNF1B gene retards the growth of the insulin-producing beta cells in the pancreas.
People with a rare inherited form of diabetes called maturity-onset diabetes of the young, type 5 (MODY5), inherit the mutated HNF1B gene from a parent and have an underdeveloped pancreas. In this study, undifferentiated or pluripotent stem cells were obtained from MODY5 patients and were compared against cells obtained from healthy controls. The team found that expression of the PAX6 gene, critical for beta cell function and insulin production, was reduced in the cells from the MODY5 population.
The study was lead by Adrian Teo, who explains, “We used MODY5 patient-specific induced pluripotent stem cells to go back in time, mimicking human pancreas development in our cell culture dish. Amazingly, we discovered that HNF1B gene mutation actually affected the development of the human pancreas very early in life.”
The team also found that a number of other pancreatic development genes were upregulated, perhaps compensating for the mutation. This compensation possibly delays the onset of diabetes in MODY5 as compared to other genetic forms that manifest as neonatal diabetes.
“By understanding the role of these beta cell genes, we can understand the mechanistic cause of diabetes. This may mean that eventually we could stratify our diabetic population into subgroups and treat them appropriately based on disease mechanism rather than just blood glucose levels”, says Teo.
With such studies providing a better understanding of the mechanisms of disease development, and technologies such as CRISPR taking big strides, it may not be unrealistic to foretell that personalized treatment strategies would dominate the future of medicine.
Original Paper: Stem Cell Reports