Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Insulin-releasing switch discovered

16.03.2011
Johns Hopkins researchers believe they have uncovered the molecular switch for the secretion of insulin — the hormone that regulates blood sugar — providing for the first time an explanation of this process.

In a report published online March 1 in Cell Metabolism, the researchers say the work solves a longtime mystery and may lead to better treatments for type 2 diabetes, the most common form of the disease.

"Before our discovery, the mechanism behind how exactly the insulin-producing beta cells in the islet of Langerhans of the pancreas fail in type 2 diabetes was incompletely understood, making it difficult to design new and better therapies, says Mehboob Hussain, M.D., associate professor of pediatrics, medicine and biological chemistry. "Our research cracks open a decades-long mystery."

After a meal, the pancreas produces insulin to move glucose from the blood into cells for fuel. People with type 2 diabetes either don't secrete enough insulin or their cells are resistant to its effects.

In a study designed to figure out more precisely how the pancreas releases insulin, Hussain's group looked at how other cells in the body release chemicals. One particular protein, Snapin, found in nerve cells, caught their eye because it's used by nerve cells to release chemicals necessary for cell communication. Snapin also is found in the insulin-secreting pancreatic beta cells.

To test the role of Snapin, researchers engineered a change to the Snapin gene in mice to keep Snapin permanently "on" in the pancreas. Researchers removed the pancreas cells and grew them in a dish for a day, then added glucose to the cells and took samples to measure how much insulin was released.

When the scientists compared that measurement to what was released by pancreas cells in normal mice, they found that normal mice released about 2.8 billionths of a gram of insulin per cell, whereas the cells from "Snapin-on" mice released 7.3 billionths of a gram of insulin per cell — about three times the normal amount.

"We were surprised to find that the Snapin-on mice didn't have more or bigger pancreas cells, they just made more insulin naturally," says Hussain. "This means all our insulin-secreting cells have this amazing reserve of insulin that we didn't really know existed and a switch that controls it."

To see if permanently turning off Snapin would reduce insulin release and further demonstrate that Snapin controls the process, the researchers first grew normal mouse pancreas cells in a dish, and treated them with a chemical that stopped them from making the Snapin protein. They again bathed the cells in glucose and measured how much insulin was released by the cells. Normal cells released 5.8 billionths of a gram of insulin, whereas cells with no Snapin only released 1.1 billionths of a gram of insulin — about 80 percent less.

"These results convinced us that Snapin is indeed the switch that releases insulin from the pancreas," says Hussain.

Normally, according to Hussain, when we ingest glucose, the pancreatic beta cells release an initial burst of insulin almost immediately, then gradually release more insulin about 15 minutes later. However, people with type 2 diabetes and mice engineered to react metabolically like people with type 2 diabetes don't release this initial spurt of insulin when fed glucose, but still have the later gradual insulin release.

"We knew how important the first burst of insulin is for controlling our blood sugar, but we did not know what really went wrong in our beta cells in people with type 2 diabetes," says Hussain. "We have drugs that restore the first burst of insulin and yet we did not completely understand how they work."

Hussain then questioned whether Snapin could be used to fix the defects in cells from a diabetic animal.

Since the cells with Snapin on made too much insulin, researchers wanted to see if they could use this to restore these mice's ability to secrete the initial burst of insulin. After growing pancreatic beta cells from type 2 diabetes mice in a dish and engineering them to make the Snapin-on protein, the researchers fed the cells glucose and found that they did indeed regain the ability to release that initial insulin burst.

"While keeping Snapin on in these mouse cells corrects the problem in this animal model of type 2 diabetes, we're still a long way from knowing if the same mechanism will work in people, but this gives us an encouraging start," says Hussain.

This study was funded by the National Institutes of Health.

Other authors on the paper are Woo-Jin Song, Madhav Seshadri, Uzair Ashraf, Thembi Mdluli and Prosenjit Mondal of the Johns Hopkins University School of Medicine; Meg Keil and Monalisa Azevedo and Constantine Stratakis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH; and Lawrence Kirschner of Ohio State University.

On the web: Cell Metabolism http://www.cell.com/cell-metabolism/

Mehboob Hussain http://www.hopkinschildrens.org/Mehboob-Ali-Hussain-MD.aspx

Pediatrics http://www.hopkinschildrens.org/index.aspx

Biological Chemistry http://biolchem.bs.jhmi.edu/pages/index.html

Vanessa McMains | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>