Did you know DNA could make eating that second piece of cake too risky?
Genetics delay the conversion of proinsulin to insulin
The year was 1922. Fourteen-year-old diabetic Leonard Thompson existed on a starvation diet of a mere 450 calories. The only treatment available for diabetes. He weighed just 65 lbs, half the weight of a healthy boy his age. Yet his blood sugar levels were still too high. He was on the brink of a diabetic coma, which appeared to be inevitable. Backed into a corner, Leonard’s dad had no choice but to accept the experimental medicine the doctors offered him. Despite that it had never been tested on a human. Two weeks later, Leonard became a medical miracle – the poster boy for “Insulin” therapy.
Since its discovery, insulin has saved and continues to save the lives of millions. This small hormone is responsible for properly regulating our blood sugar. This is why even small changes in insulin levels can increase our risk of diabetes. The MADD gene is linked to insulin production, and changes in this gene dictate how much sugar we can consume and our risk of type 2 diabetes.
Insulin is a hormone that plays a key part in our metabolism. When beta cells in the pancreas detect sugar spikes, (e.g. after a meal), they release insulin to bring our blood glucose (sugar) levels back to normal. Insulin promotes the uptake of glucose from the blood into muscle, liver and fat cells to be stored for later use.
However, the amount of insulin released into the blood needs to be carefully controlled, because both too little and too much insulin can have health implications. To be able to respond to rapid glucose changes in a timely manner, insulin reserves are kept inside beta cells. Insulin is initially synthesized as preproinsulin, which is inactive. Preproinsulin is then converted to proinsulin, a precursor of insulin. In the final step, proinsulin is processed to make insulin, which is then stored inside beta cells until needed. In essence, the production and the release of insulin happens independently of each other. However, glucose can enhance both the production and the release of insulin.
The rs7944584 variant of the MADD gene is linked to diabetes, as it affects the conversion of proinsulin to insulin. Participants in one study were given 75 grams of glucose following an overnight fast, after which the levels of insulin and proinsulin were measured every 30 minutes for 2 hours. Individuals with the variant of MADD had higher proinsulin levels, and higher proinsulin-insulin ratios. This suggests that they couldn’t effectively convert proinsulin to insulin.
Similarly, removing the MADD gene from the beta cells of mice caused hyperglycaemia (abnormally high blood glucose) by either slowing down or reducing the production of insulin. Other studies have linked rs7944584 to elevated fasting blood glucose (higher blood glucose following an overnight fast), and to an increased risk of type 2 diabetes. While several independent studies have linked rs7944584 to blood glucose levels, exactly how the protein encoded by MADD influences our susceptibility to diabetes requires further studies.
Diabetes affects more than 366 million people around the world. It is one of the fastest growing diseases of our time. At the same time, scientists have made tremendous advances in understanding the genetics behind type 2 diabetes. The MADD gene serves as an excellent therapeutic candidate for treating diabetes, and mitigating the risk associated with inheriting the defective version of this gene. Just remember — if you happen to live by the philosophy of “you only live once” when it comes to accepting that second piece of cake, you might want to find out your genetic predisposition to diabetes before it’s too late.