Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Joslin scientists show knocking out two key signals will cause diabetes

14.02.2005


Boosting these cellular signals may lead to new treatments

Using a revolutionary technique to turn off chemical signals inside the cell, scientists at Joslin Diabetes Center have discovered that the different metabolic abnormalities present in type 2 diabetes can be caused by knocking out two key signals in liver cells. Their findings in mice may someday lead to strategies in humans to boost these two different signals, providing a powerful new way to treat the different metabolic components present in the most common form of diabetes. "By lowering the level of two key insulin signaling proteins in liver cells, we began to uncover just how complex type 2 diabetes and the related metabolic syndrome are," said principal investigator C. Ronald Kahn, M.D., President of Joslin Diabetes Center and the Mary K. Iacocca Professor of Medicine at Harvard Medical School. "Both protein signals needed to be knocked out at the same time to create the full diabetic syndrome, while depleting just one or the other caused only either the glucose or the lipid abnormalities associated with diabetes. Thus, these two pathways complement each other, each controlling a part of the metabolism that is disrupted in type 2 diabetes or the metabolic syndrome."

Others involved in the study were lead author Cullen Taniguchi, M.D., Ph.D., and former Joslin researcher Kohjiro Ueki, M.D., Ph.D., now at the University of Tokyo. Published Feb. 10 in the online edition of the Journal of Clinical Investigation, the study sheds new light on a complex question: How do cells normally process the hormone insulin and what goes wrong in diabetes? An estimated 18 million Americans have type 2 diabetes, and about one-third do not even know they have the disease. In this disorder, the body does not make enough insulin or resists its effect, a phenomenon called insulin resistance. Without effective insulin, cells throughout the body are unable to convert sugar in the bloodstream to energy, resulting in chronic fatigue, thirst and other symptoms of high blood sugar. People with diabetes also have abnormalities in lipid metabolism and are two to four times more likely to have cardiovascular disease, and they run a higher risk of damage to nerve, eye, kidney and other body tissues.



Previous discoveries by Dr. Kahn’s research team provided insight about the pathway that insulin takes to stimulate cells. Insulin docks at a receptor site at the cell membrane. Once this site is activated, chemical signals pass to other proteins inside the cell, including insulin-receptor substrates (IRS). These spark a chain of other reactions. Ultimately the cell’s energy machinery is turned on.
The Joslin study focused on two of these early intracellular signaling proteins, IRS-1 and IRS-2, and especially their role in the liver, which is a key organ for both glucose and lipid metabolism. If turned off, how would that affect the onset of type 2 diabetes? And if an effect occurred, was it causative or something that just happens along the way? The researchers needed a technique to turn off the two substrates in a living organism in just one tissue at a time. Previous studies had shown that mice bred without the genes for either IRS-1 didn’t develop diabetes, while those lacking IRS-2 developed diabetes, but this was primarily because of a defect in the beta cell, so evaluating the role of the liver was impossible.

To solve this dilemma, Dr. Kahn’s team used an elegant new genetic tool in a disease study. The technique allows researchers to turn off specific signals with a virus that targets specific cell types with a kind of RNA that would interfere with the liver cells’ ability to make IRS-1 or IRS-2. The liver is the focus of considerable diabetes research because it is a major controller of metabolic functions, including those that regulate blood glucose and fat metabolism.

In the study, the effect of the RNA interference lasted one to two weeks, reducing IRS-1 and IRS-2 by up to 80 percent. By designing separate experiments, the researchers found that each substrate acts on a different part of metabolism. Low levels of IRS-1 drive cells to make more glucose, causing blood sugar to rise. Low levels of IRS-2 are linked to higher levels of blood fats such as triglycerides. Acting alone, neither causes diabetes. But when both substrates are low, diabetes results. "Our findings show what happens when we knock out these two protein signals, causing conditions to worsen," said Dr. Kahn. "The next step is to look for ways to keep their levels up, possibly leading to new ways to prevent and treat diabetes."

Marjorie Dwyer | EurekAlert!
Further information:
http://www.joslin.harvard.edu

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

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...

Im Focus: Quantum Particles Form Droplets

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...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

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,...

Im Focus: Molecules change shape when wet

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...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>