Majority of the population is vulnerable to type-2 diabetes, reveals study

Diabetes is often called a ‘lifestyle disease’ and here’s why most of us are vulnerable to it.
Diabetes is a debilitating condition. Better to keep it at bay. Image courtesy: Shutterstock
Team Health Shots Updated: 30 Oct 2023, 16:09 pm IST
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Diabetes is one of the fastest-growing disorders in the world. A large part of the population is suffering from it and this number will only go up, according to the WHO. A new study has, in fact, revealed that most of us are at risk of developing type-2 diabetes.

Scientists have found that insulin has reached an evolutionary cul-de-sac, limiting its ability to adapt to obesity and 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.

This is what the study has to say

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. 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.”

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Weiss and team looked at a subtle mutation in human insulin in relation to the insulin of other animals such as cows and porcupines. The mutant human insulin functions within the range of natural variation among animal insulins. In spite of this, the mutation has been excluded by evolution.

The answer to this paradox is that the forbidden mutation selectively blocks the folding of proinsulin and stresses beta cells.

Insulin impairment is also becoming a thing nowadays

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 resulting in eventual 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. This vulnerability underlies a rare monogenic form of diabetes and provides an evolutionary backdrop to the present obesity-related diabetes pandemic.

Experts agree that this discovery provides a key insight into a better understanding of the development of type 2 diabetes in adults and children.

“This study is a tour de force unravelling key elements of the structural biology of insulin that affect its synthesis and function. The authors highlight the fact that the insulin gene has been susceptible throughout evolution to mutations that impair insulin’s function or stress beta cells,” said Barbara Kahn, MD, George R. Minot Professor of Medicine at Harvard Medical School.

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“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,” added Kahn.

This study can contribute to improved solutions for type-2 diabetes

Director of the University of Chicago Kolver Diabetes Center Louis Philipson, MD, acknowledged that findings will shape future approaches to research in this area.

Next, the group will work to fully define the sequence determinants that make proinsulin foldable in beta cells. Their hope is that this work will eventually lead to a new category of drugs that mitigate the cellular stress caused by proinsulin’s precarious foldability and target cellular stress in beta cells, thereby preserving insulin-production for high-risk patients. (ANI)

(With inputs from ANI)

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