In humans, insulin resistance, a condition in which insulin becomes less effective at lowering blood sugar levels, coexists with hyperinsulinemia. Both are associated with atherosclerosis, the buildup of cholesterol in blood vessels that causes coronary artery disease, heart attack, and stroke.
In this condition, vascular cells could become dysfunctional because of hyperinsulinemia or because vascular cells themselves are insulin resistant, which is caused by increased insulin production from pancreatic beta cells as a compensatory mechanism to overcome insulin resistance.
Scientists have known for some time that insulin resistance and hyperinsulinemia cause increased lipids in the circulation, which indirectly leads to atherosclerosis. However, the Joslin study, published in the May issue of the journal Arteriosclerosis, Thrombosis, and Vascular Biology, shows that, without other factors such as high blood pressure and high cholesterol, hyperinsulinemia alone does not cause atherosclerosis.
"For years, scientists have suspected that high levels of insulin could affect vascular cells negatively," says lead author Christian Rask-Madsen, MD, PhD, a research associate at Joslin's Dianne Nunnally Hoppes Laboratory for Diabetes Complications. "We know that people with type 2 diabetes and insulin resistance are susceptible to atherosclerosis, but our study shows that excess insulin alone does not promote this complication."
To study the effects of hyperinsulinemia on atherosclerosis, Rask-Madsen and his colleagues created mice with fewer insulin receptors in every tissue of the body and compared them to mice with intact insulin receptors. Insulin receptors make cells responsive to insulin, a hormone that circulates in the bloodstream. Both sets of mice were genetically modified to have high cholesterol, but were similar in terms of body weight, glucose metabolism, and lipid and blood pressure levels.
Reducing the insulin receptors from one set of mice did not significantly impair their glucose metabolism, says Rask-Madsen—certainly not enough to make the animals overtly insulin resistant—but it did increase the amount of circulating insulin by reducing its removal from the blood. This model allowed the researchers to study the effects of hyperinsulinemia without the confounding effects of insulin resistance.
The new findings build on a 2010 study conducted by Rask-Madsen, which found that insulin resistance only in endothelial cells is sufficient to increase susceptibility to atherosclerosis. George King, MD, Joslin's chief scientific officer, is the senior author of both studies.
Taken together, Rask-Madsen says, the findings of the two studies suggest that "when we look at new ways to prevent atherosclerosis, we should focus on improving insulin signaling in vascular cells rather than blocking the action of insulin in these cells."
Contributors to the paper include Joslin's Erica Buonomo, Qian Li, Kyoungmin Park, Allen Clermont and Oluwatobi Yerokun, and Mark Rekhter of Lilly Research Laboratories. Funding came from the National Institutes of Health.
About Joslin Diabetes Center
Joslin Diabetes Center, located in Boston, Massachusetts, is the world's largest diabetes research and clinical care organization. Joslin is dedicated to ensuring that people with diabetes live long, healthy lives and offers real hope and progress toward diabetes prevention and a cure. Joslin is an independent, nonprofit institution affiliated with Harvard Medical School.
Our mission is to prevent, treat and cure diabetes. Our vision is a world free of diabetes and its complications.
Keep up with Joslin research and clinical news at Inside Joslin at http://www.joslin.org/news/inside_joslin.html,
Become a fan of Joslin on Facebook at http://www.facebook.com/joslindiabetes
Follow Joslin on Twitter @JoslinDiabetes
Jeffrey Bright | EurekAlert!
Chronic stress induces fatal organ dysfunctions via a new neural circuit
21.08.2017 | Hokkaido University
New malaria analysis method reveals disease severity in minutes
14.08.2017 | University of British Columbia
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
21.08.2017 | Materials Sciences
21.08.2017 | Health and Medicine
21.08.2017 | Materials Sciences