Scientists from Indiana University School of Medicine, the University of Michigan, and the University of Case Western Reserve District have revealed that most people are vulnerable to type 2 diabetes. The reason is the evolution of insulin, as a result of which the synthesis of the hormone and its functions are prone to disruption. The main cause of the development of metabolic disease is reported in an article published in the journal Proceedings of the National Academy of Sciences.
Insulin is produced through processes in specialized cells called beta cells in the pancreas. The insulin precursor, proinsulin, collapses, acquiring the desired structure and the ability to perform the desired functions. It consists of an A-chain and a B-chain, which are connected to each other by a C-chain. When proinsulin is converted to insulin, the C-chain is cut, and the A-chain and B-chain are hooked to each other by disulfide bridges. Moreover, in vertebrates, the amino acid phenylalanine should be in the 24th position of the B-chain.
Even if phenylalanine is replaced by tyrosine, which differs from the first only in the presence of a hydroxyl group (OH), then proinsulin biosynthesis will be disrupted and beta cells will be damaged. However, despite the violation, in solution, this version of proinsulin folds into insulin TyrB24, which can perform the same functions as ordinary insulin. This is due to the fact that phenylalanine is only important at an intermediate stage in insulin synthesis.
According to the findings of scientists, it is this insecurity of the hormone that makes humans evolutionarily vulnerable to diabetes. Insulin is in a kind of evolutionary dead end, since no mutation can positively affect both the synthesis and the effectiveness of the hormone when binding to the receptor. All of these functions require different structural features that conflict with each other. For example, in type 2 diabetes, excess hormone contributes to progressive dysfunction of beta cells, and evolution simply cannot fix this, since such a fix is associated with a deterioration in other hormone function.
