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Most People Are Susceptible To Type 2 Diabetes
This group sought to determine if the evolution of insulin in vertebrates - including humans -- has encountered a roadblock. Has a complex series of steps imposed constraints that have frozen the sequence of insulin at a precipice of non-foldability?
By: Hunan Huateng Pharmaceutical Co. Ltd.
Insulin is produced by a series of highly specific processes that occur in specialized 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. Has a complex series of steps imposed constraints that have frozen the sequence of insulin at a precipice of non-foldability?
According to the study published in the Proceedings of the National Academy of Sciences, the answers are yes and yes.
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.
The group discovered that even the slightest variation of the insulin-sequencing process not only impairs insulin folding (and eventual insulin secretion) but also induces cellular stress that leads to beta cell dysfunction and eventually permanent damage.
Weiss said that the study highlights the importance of folding efficiency as a critical but hidden factor in the evolution of insulin over the past 540 million years. Humans have evolved to be vulnerable to diverse mutations in the insulin gene and that this vulnerability underlies a rare monogenic form of diabetes and provides an evolutionary backdrop to the present obesity-related diabetes pandemic.
Huateng Pharma (https://en.huatengsci.com/