Study suggests most humans are vulnerable to Type 2 diabetes

Scientists have found that insulin has met an evolutionary cul-de-sac, limiting its ability to adapt to obesity and thereby rendering most people vulnerable to Type 2 diabetes. A recent study from scientists at Indiana University School of Medicine, the University of Michigan and Case Western Reserve University has determined that the sequence of insulin has become entrenched at the edge of impaired production, an intrinsic vulnerability unmasked by rare mutations in the insulin gene causing diabetes in childhood. The study exploits biophysical concepts and methods to relate protein chemistry to the emerging field of evolutionary medicine. Insulin is produced by a series of highly specific processes that occur in specialised cells, called beta cells. A key step is the folding of a biosynthetic precursor, called proinsulin, to achieve the hormone's functional three-dimensional structure. Past studies from this and other groups have suggested that impaired biosynthesis could be the result of diverse mutations that hinder the foldability of proinsulin. This group sought to determine if the evolution of insulin in vertebrates--including humans--has encountered a roadblock. According to the study published in the Proceedings of the National Academy of Sciences, the answers are yes and yes."Biological processes ordinarily evolve to be robust, and this protects us in the majority of cases from birth defects and diseases," said Michael Weiss, MD, PhD, Distinguished Professor at IU School of Medicine and lead investigator of the study. "Yet diabetes seems to be an exception."Weiss and team looked at a subtle mutation in human insulin in relation to the insulins of other animals, such as cows and porcupines. The mutant human insulin functions within the range of natural variation among animal insulins, and yet this mutation has been excluded by evolution.