Washington, October 2 : A team of researchers from the University of Michigan Medical School have found that the cells that make insulin in the body of people with diabetes may stop this task because of glitches in the production of a molecule called proinsulin, the precursor out of which insulin is made.

The cells that produce insulin in the body are called beta cells. They normally churn out large quantities of insulin within the pancreas, which is then released into the bloodstream as needed, to help the body turn sugars from food into energy for cells.

However, in people with diabetes, the beta cells do not keep up with the demand for insulin, and sugar builds up in the blood, wreaking havoc on nerves, blood vessel walls and kidneys. This worsens the progression of the disease.

Now, the researchers have found that beta cell dysfunction may occur as a result of problems in the production of a molecule called proinsulin, which in turn can lead to the start, or progression, of diabetes.

"We believe that in the insulin production factory, misfolded copies of newly-made proinsulin can gum up the works in several ways. This paper shows that one of the first things that can happen is that misfolded proinsulin can stick to other proinsulin in the very first stages of production within the endoplasmic reticulum,” said Dr. Peter Arvan, senior author of the study published in the Proceedings of the National Academy of Sciences.

He revealed that this chain reaction can start with just a few misfolded proinsulin molecules, and thereby can lead to beta cell shutdown and an insulin shortage.

“The misfolded proinsulin does not get exported from the factory, and neither does the normally folded proinsulin made after it. Pretty soon, pancreatic beta cells are running out of insulin to secrete in response to the customer's demand for the product – that is, an increase in blood glucose,” he said.

Arvan revealed that his team inserted the human gene into rat pancreas cells, which allowed them to see the human proinsulin being made in live rat cells under the microscope. Thereafter, the researchers introduced a mutation into the tagged human insulin gene that caused the proinsulin molecule to fold incorrectly, he added.

He said that this allowed the researchers to see what happened when the misfolded human proinsulin and the normal rat proinsulin were produced together inside the same cell.

The Arvan lab is now collaborating with several other research groups to identify new mutations in the proinsulin gene of people with congenital diabetes, and to understand how these mutations may cause a similar “protein mess.”

“The big question -- still to be determined -- is how much of the more common forms of diabetes also involve proinsulin misfolding in beta cells that are stressed to the max to make all the insulin they can. This is a question that we are actively pursuing,” he said. (With inputs from ANI)

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