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
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
19.07.2018 | Materials Sciences
19.07.2018 | Earth Sciences
19.07.2018 | Life Sciences