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!
Infants later diagnosed with autism follow adults’ gaze, but seldom initiate joint attention
24.05.2019 | Schwedischer Forschungsrat - The Swedish Research Council
When wheels and heads are spinning - DFG research project on motion sickness in automated driving
22.05.2019 | Technische Universität Berlin
A new assessment of NASA's record of global temperatures revealed that the agency's estimate of Earth's long-term temperature rise in recent decades is accurate to within less than a tenth of a degree Fahrenheit, providing confidence that past and future research is correctly capturing rising surface temperatures.
The most complete assessment ever of statistical uncertainty within the GISS Surface Temperature Analysis (GISTEMP) data product shows that the annual values...
Physicists at the University of Basel are able to show for the first time how a single electron looks in an artificial atom. A newly developed method enables them to show the probability of an electron being present in a space. This allows improved control of electron spins, which could serve as the smallest information unit in a future quantum computer. The experiments were published in Physical Review Letters and the related theory in Physical Review B.
The spin of an electron is a promising candidate for use as the smallest information unit (qubit) of a quantum computer. Controlling and switching this spin or...
Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...
With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.
Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...
'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.
However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...
29.04.2019 | Event News
17.04.2019 | Event News
15.04.2019 | Event News
24.05.2019 | Physics and Astronomy
24.05.2019 | Medical Engineering
24.05.2019 | Life Sciences