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Most humans at risk of type 2 diabetes as evolution of insulin hits roadblock

Most humans at risk of type 2 diabetes as evolution of insulin hits roadblock
The authors of this study highlight the fact that the insulin gene has been susceptible throughout evolution to mutations that impair insulin's function or stress beta cells. @Shutterstock

The insulin gene has been susceptible throughout evolution to mutations that impair insulin's function or stress beta cells. Read on to know more.

Written by Jahnavi Sarma |Published : November 7, 2020 5:12 PM IST

Type 2 diabetes is a chronic health condition where your body is not able to use the hormone insulin the way it is supposed to. Your body develops insulin resistance and it leads to high levels of sugar in your bloodstream. It is also called adult onset diabetes and middle-aged and older people are likely to develop this condition. But now, because of obesity and environmental factors, even children and adolescents are becoming prey to this disease.

Insulin is an important hormone in the human body. The evolution of insulin in vertebrates -- including humans -- has encountered a roadblock, limiting its ability to adapt to obesity and thereby rendering most people vulnerable to type 2 diabetes, a significant research has claimed. Scientists from Indiana University (IU), University of Michigan and Case Western Reserve University 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.

Biological processes behind this roadblock

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 have suggested that impaired biosynthesis could be the result of diverse mutations that hinder the foldability of proinsulin. Biological processes ordinarily evolve to be robust, and this protects us in the majority of cases from birth defects and diseases. Yet, diabetes seems to be an exception.

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Cellular stress causes beta cell dysfunction

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. The study, published in the Proceedings of the National Academy of Sciences, highlights the importance of folding efficiency as a critical but hidden factor in the evolution of insulin over the past 540 million years.

Understanding of the pathogenesis of type 2 diabetes

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. The authors of this study highlight the fact that the insulin gene has been susceptible throughout evolution to mutations that impair insulin's function or stress beta cells. As we approach the 100th anniversary of the discovery of insulin, these elegant observations might lead to a better understanding of the pathogenesis of Type 2 diabetes. The group will work to fully define the sequence determinants that make proinsulin foldable in beta cells.

Common symptoms of type 2 diabetes

Symptoms of this condition is sometimes so subtle that it may be difficult to recognize them. Most of the time, a doctor may diagnose this condition when you go for a general check-up for some other illness. But some common signs of type 2 diabetes are unnatural thirst, increased frequency of urination, blurry vision and mood swings. You may also experience a tingling or numbness in your hands or feet and a general sense of tiredness. Wounds may take a longer time to heal and you may be more hungry than usual. Sudden weight loss and frequent infections may also occur, and you may notice the skin around your neck or armpits changing colour.

(With inputs from IANS)