protein

Scientists find proteins that reveal another piece of the diabetes puzzle

by Barbara Hewitt on July 7, 2016

Proteins that play key roles in the timing of cell division also play a key part in regulating blood sugar levels and could help scientists understand more about type 2 diabetes.

The main framework of insulin signalling has been known for decades, but now researchers from the University of Texas Southwestern Medical Center have identified a major, new regulatory mechanism of this important cell signalling pathway.

microbiologist-lab-scientistIt is effectively a piece of the diabetes puzzle, according to senior author Dr. Hongtao Yu, Professor of Pharmacology at UT Southwestern and an investigator with the Howard Hughes Medical Institute (HHMI).

The study found that three ‘spindle checkpoint’ proteins long associated with the timing of cell division are central to the newly identified mechanism that regulates insulin signalling,

Dr. Eunhee Choi, a research scientist in the Yu laboratory and lead author of the study, explained that while in type 1 diabetes the pancreas is unable to produce insulin, in type 2 diabetes the body produces insulin but is unable to respond to it, a condition called insulin resistance.

It has long been known that insulin sends signals from the outside to the inside of the cell via insulin receptors located on the cell surface. The receptors have two ‘arms’ that extend outside the cell and two ‘arms’ that reach into the cell’s interior.

Under normal conditions, insulin is secreted after a meal and binds to insulin receptors throughout the body. That binding activates the receptors, which then send signals inside the cells to take up, or clear, glucose from the bloodstream, keeping blood sugar in balance. Once the receptors have done their job, they are drawn into the cell in a process called endocytosis so that new receptors can take their place on the cell’s surface in an elegant and precisely timed process that is repeated several times a day.

The researchers were studying another process, cell division with its careful partitioning of the genetic blueprint contained in chromosomes, when the scientists came upon an unexpected link between the two fundamental processes.

‘When studying the functions of spindle checkpoint proteins known to regulate chromosome segregation during cell division, we unexpectedly discovered that these cell division proteins can moonlight to regulate the endocytosis of insulin receptors,’ Dr. Yu said.

He explained that the three proteins they studied are crucial for accurate timing of chromosome partitioning during cell division. If the cells fail to divide at just the right time, the resulting daughter cells will have the wrong number of chromosomes, a situation called aneuploidy that often occurs in cancer cells, he said.

They found that the three proteins that are key to timing in cell division also seem to affect metabolism via timing, specifically through their impact on insulin receptors.

‘Our study provides an example of how an entire branch of key regulatory proteins in one important biological process (cell division) can be enlisted to control another biological process (insulin signalling). Similar molecular interactions among these proteins are used in both cases, with remarkable mechanistic parallels,’ Dr. Yu said, adding that these findings may have implications in deciphering the molecular underpinnings of type 2 diabetes, in which insulin is produced but patients fail to respond to the hormone for reasons that are being actively investigated.

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