Study links proteins involved in cell division in insulin signaling

Study links proteins involved in cell division in insulin signaling -

The proteins that play a key role in the timing of cell division as clear moon in regulation sugar levels in the blood, researchers at UT Southwestern Medical Center have found.

"The main part of insulin signaling has been known for decades, and no new major regulations were found in recent years. Defying the odds, we have identified a large, new mechanism regulating this important cell signaling pathway, "said study senior author Dr. Hongtao Yu, professor of pharmacology at UT Southwestern and an investigator with the Howard Hughes Medical Institute (HHMI).

study , published online today in cell , found that three proteins "spindle checkpoint" long associated during cell division are at the center of the newly identified mechanism that regulates signaling the insulin, said Dr. Yu, who holds the Chair Emeritus Serena S. Simmons in immuno-pharmacology and cancer. a Michael L. Rosenberg Scholar in Medical Research

The World Health Organization estimates that diabetes - a serious metabolic disease public health problem - affects over 400 million people worldwide. The condition disrupts the body's ability to keep blood sugar (glucose) in balance. Over time, elevated blood sugar levels can damage nerves and blood vessels throughout the body.

There are two main forms of diabetes. In type 1 diabetes, the pancreas is unable to produce insulin. In type 2 diabetes, the body produces insulin but is unable to answer, a condition called insulin resistance, said Dr. Eunhee Choi, researcher in the Yu laboratory and lead author of the study.

It has long been known that insulin sends signals outside towards the inside of the cell by insulin receptors located on the cell surface. receptors have two "arms" that extend outside of the cell and two "arms" that reach the interior of the cell, Dr. Choi said.

Under normal conditions, insulin is secreted after a meal and binds to insulin receptors throughout the body. This operative connection receptors, which then send signals within the cells to be taken, or clear glucose from the bloodstream, keeping blood glucose levels in balance. Once the receivers did their job, they are drawn into the cell in a process called endocytosis so new receivers can take their place on the surface of the cell in an elegant process and timed precisely which is repeated several times a day Dr. Yu said.

His laboratory studies another process - cell division with its careful partitioning of the genetic blueprint contained in the chromosomes -. when scientists came to 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 discovered unexpectedly these cell division proteins can moonlight to regulate the endocytosis of insulin receptors, "said Dr. Yu.

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

the Yu laboratory, who studied spindle checkpoint control in cell division protein for over a decade, studied mice missing one of three proteins (p31 ^comet ) in their liver. Researchers should whether a potential model of aneuploidy and possibly cancer, diabetes but instead, the mice developed.

The further investigation, they found that the three proteins that are essential for the time of cell division also seem to affect the metabolism via the calendar, particularly through their impact on the receivers insulin, he said. Mice that lack p31 ^comet in the liver can not keep insulin receptors on the cell surface, due to premature endocytosis.

"Our study provides an example of how an entire branch of key regulatory proteins important biological processes (cell division) can be enlisted to control other biological processes (insulin signaling). Similar molecular interactions between these proteins are used in both cases, with remarkable mechanistic parallel, "said Dr. Yu, adding that these findings may have implications in deciphering the molecular basis of type 2 diabetes, in which insulin is produced, but patients fail to respond to the hormone for reasons that are actively considering.

"It will be interesting to examine whether insulin receptor endocytosis premature arising from defective p31 ^Comet contributes to insulin resistance in patients with type 2 diabetes" he said. Future studies are planned to explore that possibility.