The University of Wisconsin–Madison researchers’ efforts, published Oct. 6 in the journal PLoS Genetics, pinpointed a gene that confers diabetes susceptibility in obese mice.
They also showed that the protein coded by the gene, called tomosyn-2, acts as a brake on insulin secretion from the pancreas.
“It’s too early for us to know how relevant this gene will be to human diabetes,” says Attie, a UW–Madison biochemistry professor, “but the concept of negative regulation is one of the most interesting things to come out of this study and that very likely applies to humans.”
In a properly tuned system, insulin secreted into the blood after eating helps maintain blood sugar at a safe level. Too little insulin (as in type 1 diabetes) or insulin resistance (as in type 2 diabetes) leads to high blood sugar and diabetic symptoms. Too much insulin can drive blood glucose dangerously low and lead to coma or even death in a matter of minutes.
“You can imagine that if you’re in a fasted state, you don’t want to increase your insulin, so it’s very important to have a brake on insulin secretion,” says Angie Oler, one of the lead authors. “It needs to be stopped when you’re not eating and it needs to start again when you do eat.”
The group honed in on tomosyn-2 while searching for genes that contribute to diabetes susceptibility in obese animals.
Why study fat mice?
“It takes more insulin to achieve the same glucose-lowering effect in an obese person than it does in a lean person. If you can produce that extra insulin – and most people do – you’ll be okay. You will avoid diabetes at the expense of having to produce and maintain a higher insulin level,” Attie explains. “Most of the type 2 diabetes that occurs in humans today would not exist were it not for the obesity epidemic.”
But an insufficient insulin response leads to diabetes, and the same is true in mice.
Painstaking genetic analyses and comparisons of obese diabetes-resistant and diabetes-susceptible mouse strains ultimately revealed a single amino acid difference that destabilizes the tomosyn-2 protein in the diabetes-resistant mice, effectively releasing the brake on insulin secretion and allowing those animals to release enough insulin to avoid diabetes.
The researchers also confirmed that the human form of tomosyn-2 inhibits insulin secretion from human pancreatic beta cells.
Though diabetes is highly unlikely to be caused by a single gene, identifying important biological pathways can suggest clinically useful targets. “This study shows the power of genetics to discover new mechanisms for a complex disease like type 2 diabetes,” says postdoctoral fellow Sushant Bhatnagar, a co-lead author of the paper.“Now we know there are proteins that are negative regulators of insulin secretion. Very likely they do the same thing in human beta cells, and it motivates us to move forward to try to figure out the mechanisms behind that negative regulation,” Attie says.
The American Diabetes Association and the National Institutes of Health provided research funding.Jill Sakai, email@example.com, (608) 262-9772
Jill Sakai | Newswise Science News
Nonstop Tranport of Cargo in Nanomachines
20.11.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik
Researchers find social cultures in chimpanzees
20.11.2018 | Universität Leipzig
Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.
Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
20.11.2018 | Life Sciences
20.11.2018 | Life Sciences
20.11.2018 | Physics and Astronomy