Studies suggest that most humans are vulnerable to type 2 diabetes

Scientists have discovered that insulin encounters an evolutionary dead end, limiting its ability to adapt to obesity, thereby making most people vulnerable to type 2 diabetes.

In a recent study by scientists at Indiana University School of Medicine, University of Michigan, and Case Western Reserve University, Insulin Established at the edge of production failures, revealing intrinsic vulnerabilities Rare mutation Of the insulin gene that causes diabetes in childhood. This study leverages biophysical concepts and methods to link protein chemistry to new areas of evolutionary medicine.

Insulin is produced by a series of highly specific processes that occur in specialized cells. Beta cells.. An important step is to fold a biosynthetic precursor called proinsulin to achieve the functional three-dimensional structure of the hormone. Previous studies in this and other groups suggest that impaired biosynthesis may be the result of a variety of mutations that impede the folding of proinsulin.

This group sought to determine if insulin evolution in vertebrates, including humans, was impaired. Did the complex sequence of steps impose the constraint of freezing the insulin sequence on an unfoldable cliff? If so, did this leave humanity vulnerable to type 2 diabetes as a pandemic disease of civilization?

According to a study published in Minutes of the National Academy of Sciences, The answer is yes and yes.

“Biological processes usually evolve robustly, which in most cases protects us from congenital deficiencies and illnesses,” said Michael, a prominent professor and principal investigator at IU School of Medicine. Dr. Weiss said. “But diabetes seems to be an exception.”

Weiss and his team investigated subtle mutations in human insulin in the context of insulin in other animals such as cattle and porcupines. Mutant human insulin functions within the natural variation between animal insulins, but this mutation has been eliminated by evolution. The answer to this seemingly paradox is that forbidden mutations selectively block proinsulin folds and stress beta cells.

In this group, even the slightest changes in the insulin sequencing process impair insulin folding (and ultimate insulin secretion), as well as cellular stress leading to beta cell dysfunction and ultimately permanent damage. Was found to induce.

Weiss, chair of the Biochemistry and Molecular Biology Division and a professor of the Precision Health Initiative, said the study found folding efficiency as an important but hidden factor in the evolution of insulin over the last 540 million years. He said he emphasized the importance. Humans have evolved to be vulnerable to various mutations in the insulin gene, which underlies rare single-genotype diabetes and has evolved into the current obesity-related diabetes epidemic. Provides a background for.

Experts from around the world agree that this finding provides important insights into a better understanding of the development of type 2 diabetes in adults and children, which is rising at an alarming rate in Indiana and around the world. I will.

“This study is a tour to elucidate key elements of the structural biology of insulin that affect insulin synthesis and function,” said Dr. Barbara Khan, professor of medicine at Harvard Medical School, George R. Minott. Stated. “The authors emphasize the fact that insulin genes are susceptible to mutations that impair insulin function or stress beta cells throughout evolution. As we approach the 100th anniversary of insulin discovery, these elegant Observations may lead to a better understanding of the etiology of type 2 insulin. “

Dr. Louis Philippe, MD, director of the University of Chicago Colver Diabetes Center, agreed, adding that the findings would shape a future approach to research in this area.

“Current findings define a major problem for the future. The harmful misfolding of proinsulin found in patients with INS mutations is also probably at lower levels, but broader in human type 2. Whether it can occur in groups. Diabetes Patients all over the world. “

The group then works to fully define the sequencing factors that make proinsulin foldable in beta cells. Their hope is that this study will ultimately reduce the cellular stress caused by the unstable folding properties of proinsulin, target beta cell cellular stress, and thereby maintain insulin production in high-risk patients. It is to lead to a category of drugs.