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
Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel
The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
05.12.2016 | Power and Electrical Engineering
05.12.2016 | Materials Sciences
05.12.2016 | Power and Electrical Engineering