One Gene Protects Against Type 2 Diabetes
A mutation in one gene has been found to protect people from the onset of type 2 diabetes.
Type 2 diabetes is caused by the inability of the body to regulate its blood sugar levels, as the cells are unable to produce or respond to the hormone insulin. Type 2 diabetes affects over 400 million people worldwide, and disease onset can be caused by both genetic and lifestyle factors. A mutation in the SLC30A8 gene, found in 0.02% of the European population, reduces the risk of diabetes, but it is not understood why.
SLC30A8 is highly expressed in pancreatic B cells, which produce and secrete insulin. Insulin stimulates cells to take up glucose and convert it to glycogen, which lowers blood sugar levels. The SLC30A8 gene codes for a protein that carries zinc across the membrane into the B cells to enable the crystallisation and storage of insulin.
Interestingly, the SLC30A8 mutation is more common in Finland than the general European population. Finnish people with the mutation were recruited for the study, as were their relatives. By comparing people who had the mutation to their relatives, who may or may not have the mutation, it is possible to isolate the effect of the SLC30A8 gene on diabetes type 2 onset. Participants were measured for their ability to regulate glucose, known as glucose tolerance. After a meal, their blood glucose and insulin levels were recorded over time. People with the mutation had higher insulin levels and lower blood sugar, demonstrating that they could return their blood sugar levels to normal more effectively.
A knockdown of SLC30A8 in human B cells reduces ZnT8 protein production, which leads to increased insulin secretion. There is also evidence for the mutation promoting the conversion of conversion of the prehormone proinsulin to insulin. The mutation appears to strongly influences beta cell development and increases the cells ability to produce insulin.
Targeting the ZnT8 protein could therefore be a potential target for preventing the onset of type 2 diabetes.
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