Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cedars-Sinai researchers identify a gene that causes insulin resistance in Mexican Americans

29.12.2003


A condition linked to heart disease, diabetes, high blood pressure and obesity

For over a decade, scientists have known that insulin resistance - a syndrome where the body does not respond as well as it should to insulin - is linked to the development of heart disease, diabetes, high blood pressure, obesity and polycystic ovary syndrome. In fact, one in four adult Americans has insulin resistance, with Mexican Americans having the highest prevalence. But because people with insulin resistance are so likely to develop diseases such as diabetes and heart disease, scientists have turned their attention on investigating whether a common gene abnormality may be involved.

Now, researchers at Cedars-Sinai Medical Center, in collaboration with investigators at UCLA, have found that lipoprotein lipase (LPL), a gene that controls the delivery of fatty acids to muscle and tissues in the body, is linked to insulin resistance in Mexican-Americans. Their findings, reported in the January issue of Diabetes, may enable scientists to design therapies that target LPL to prevent insulin resistance, a condition estimated to affect over 80 percent of the 16 million Americans with Type 2 diabetes, and additional millions at risk for heart disease.



"This is the first study to definitively show that LPL is a gene for common insulin resistance," said Jerome I. Rotter, M.D., Director of the Division of Medical Genetics and Director of the Common Disease Genetics Program at Cedars-Sinai Medical Center.

In recent years, LPL has emerged as a likely "gene candidate" to study for insulin resistance because some studies had linked it to high blood pressure, obesity, and atherosclerosis (fatty deposits in the arteries) - all of which are associated with the insulin resistance syndrome. But the studies were small, used limited diagnostic tests, and looked at only small portions of the LPL gene.

To determine whether LPL was directly linked to insulin resistance, researchers under Dr. Rotter’s direction, conducted the first study to examine a large, high-risk population of Mexican-Americans using the most precise diagnostic and genetic tests: the glucose clamp, the most precise diagnostic test, coupled with an analysis of the patients’ DNA for a group of six of the most common LPL gene markers in this population called haplotypes. As markers of LPL, these haplotypes function similar to a "bar code" and identify all the major variations or differences of LPL in a population that could be associated with disease. In this study of Mexican-Americans, eight different haplotypes were observed.

In the study, 291 adult-offspring of parents with documented heart disease (112 men and 179 women) were tested for six specific LPL markers and underwent the glucose clamp test receiving an infusion of insulin in one arm over a two-hour period. The patients then also had blood samples drawn from the other arm to determine how much glucose was present in the blood. The patient was found to be less insulin resistant when the samples showed low blood sugar levels even when glucose was added, indicating that the cells were taking up glucose. However, if little or no glucose needed to be added, then the patient was insulin resistant because blood sugar levels were too high, indicating that cells were not using it as they should.

"The glucose clamp technique is considered the ’gold standard’ for testing insulin resistance because it provides the most direct assessment of insulin’s action as opposed to simpler tests that measure glucose or insulin levels while the patient is fasting," commented Dr. Rotter.

To determine whether insulin resistance, as measured by the glucose clamp, was linked to certain variations or haplotypes on the LPL gene, the investigators then examined the level of insulin resistance for each of the eight LPL haplotypes observed in this population. They found that one particular haplotype (designated as Haplotype 4) was associated with a high level of insulin resistance, while another haplotype (Haplotype 1) was linked with low levels of insulin resistance.

"Our study showed that two separate haplotypes of LPL were linked to low or high levels of insulin resistance, confirming that the LPL gene plays a role in determining insulin resistance in this population of Mexican Americans," said Dr. Rotter.

The investigators analyzed larger portions (haplotypes) of the LPL gene, instead of looking at only one or two variations (polymorphisms) in the gene because haplotypes represent the majority of common variation passed down in families, encompassing sections of the gene that have remained unbroken by evolution over time. Consequently, haplotypes are more likely to identify disease associations than single gene variations. Among the 291 patients typed for LPL haplotype markers, 40 patients were found to carry Haplotype 4, the gene marker linked to insulin resistance, while 239 carried Haplotype 1, which is associated with a low level of insulin resistance.

"This finding is significant because it provides direct evidence that LPL is an insulin resistance gene by showing that LPL haplotypes are linked with a direct quantitative measurement of insulin resistance in Mexican Americans," said Dr. Rotter. "The strength of this investigation is that we examined a population at high risk for the insulin resistance syndrome, that we directly measured insulin sensitivity by the glucose clamp study, and that we combined this with the power of a haplotype-based analysis."

Future studies will investigate the actual variation in the LPL gene and how it influences insulin resistance.

Cedars-Sinai Medical Center is one of the largest non-profit academic medical centers in the Western United States. For the fifth straight two-year period, Cedars-Sinai has been named Southern California’s gold standard in health care in an independent survey. Cedars-Sinai is internationally renowned for its diagnostic and treatment capabilities and its broad spectrum of programs and services, as well as breakthrough in biomedical research and superlative medical education. Named one of the 100 "Most Wired" hospitals in health care in 2001, the Medical Center ranks among the top 10 non-university hospitals in the nation for its research activities.

Sandra Van | Van Communications
Further information:
http://www.csmc.edu/

More articles from Health and Medicine:

nachricht A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital

nachricht Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München

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: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>