Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover how a high-fat diet causes type 2 diabetes

29.12.2005


Howard Hughes Medical Institute researchers have discovered a molecular link between a high-fat, Western-style diet, and the onset of type 2 diabetes. In studies in mice, the scientists showed that a high-fat diet disrupts insulin production, resulting in the classic signs of type 2 diabetes.



In an article published in the December 29, 2005, issue of the journal Cell, the researchers report that knocking out a single gene encoding the enzyme GnT-4a glycosyltransferase (GnT-4a ) disrupts insulin production. Importantly, the scientists showed that a high-fat diet suppresses the activity of GnT-4a and leads to type 2 diabetes due to failure of the pancreatic beta cells.

The experiments point to a mechanistic explanation for why failing pancreatic beta cells don’t sense glucose properly and how that can lead to impaired insulin production, said Jamey Marth, a Howard Hughes Medical Institute investigator at the University of California, San Diego (UCSD). Marth and first author Kazuaki Ohtsubo at UCSD collaborated on the studies with researchers from the Kirin Brewery Co. Ltd., and the University of Fukui, both in Japan.


The discovery of the link between diet and insulin production offers new information that may aid in the development of treatments that target the early stages of type 2 diabetes. In its earliest phases, the disease causes failure of insulin-secreting beta cells in the pancreas, which leads to elevated blood glucose levels. As the disease progresses, the insulin-secreting beta cells overcompensate for the elevated blood glucose, and eventually pump out too much insulin. This leads to insulin resistance and full-blown type 2 diabetes.

The new studies suggest that people with an inherited predisposition to type 2 diabetes might have variations in the gene for GnT-4a, said the researchers. Worldwide, more than 200 million people have type 2 diabetes, and close to 20 million people in the United States have been diagnosed with the disorder.

Marth and his colleagues began their studies hoping to learn more about the function of protein glycosylation in the pancreas. They focused on the function of GnT-4a, in part, because it is highly expressed in the pancreas. GnT-4a is a type of enzyme known as a glycosyltransferase that attaches sugar-like molecules called glycans to proteins in a process called glycosylation. Glycans are essential for the proper function of many proteins.

GnT-4a was known to maintain glucose transporters on the surface of beta cells in the pancreas. Those transporters, such as Glut-2, play a crucial role in allowing the beta cell to sense how much glucose is in the blood. Transport of glucose across the cell membrane into pancreatic beta cells triggers insulin secretion.

The new studies showed that in the absence of sufficient GnT-4a enzyme, Glut-2 lacks an attached glycan that is required for it to be expressed at the cell membrane. Without that glycan, Glut-2 leaves the cell surface and becomes internalized, where it can no longer transport glucose into the cell. In turn, this failure impairs insulin secretion, causing type 2 diabetes in the mice.

"What was really astounding to us, however, was that when we fed normal mice a high-fat diet, we saw this same mechanism of pathogenesis with attenuation of GnT-4a enzyme levels, reduced Glut-2 glycosylation, and loss of cell surface Glut-2 expression," said Marth. "This finding may explain the loss of Glut-2 commonly observed in type 2 diabetes. For example, transcriptional control of GnT-4a expression may underlie the pathogenesis of type 2 diabetes in human mature onset diabetes of the young (MODY), and perhaps in response to leptin signaling deficiency in db mice."

In addition, variations in susceptibility to type 2 diabetes may result from inherited differences in the gene for GnT-4a that may ultimately affect its level or activity. These findings could have important clinical implications because reduced GnT-4a expression has been observed by other researchers in tissue samples from humans with diabetes. "If you could somehow stimulate production of this enzyme, you might be able to render animals, and perhaps humans, resistant to high-fat diet-induced diabetes," said Marth.

To explore such possible clinical applications, Marth and his colleagues are now testing whether over-expression of the GnT-4a gene in transgenic mice makes them resistant to diabetes induced by a high-fat diet or by transcriptional factor mutations that cause MODY.

"If our findings can be applied to humans, they should give us important insights into how type 2 diabetes may be prevented and treated," he said.

While a deficiency of insulin can cause diabetes, too much insulin can also be harmful, and has been found to contribute to the pathogenesis of cancer, cardiovascular disease, ovarian diseases, and Alzheimer’s disease. "It may be that suppressing insulin production to some degree could be beneficial in such disorders, and that could theoretically be achieved by inhibiting the GnT-4a glycosyltransferase," Marth said.

Jim Keeley | EurekAlert!
Further information:
http://www.hhmi.org

More articles from Health and Medicine:

nachricht Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

nachricht Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>