The findings, which appear in the Online Early Edition of the Proceedings of the National Academy of Sciences (PNAS) this week, offer a possible new prototype for therapies to restore normal blood glucose levels in diabetes patients and suggest a previously unrecognized role for inflammation in the disease.
“Type 1 diabetes is known to develop as a consequence of autoimmune destruction of insulin-producing pancreatic beta cells,” explains senior author Terry Strom, MD, Director of the Transplantation Research Center at BIDMC and Professor of Medicine at Harvard Medical School. “But in addition to the long-recognized role of T-cell-dependent immune-system-mediated islet destruction, this work reveals for the first time that a form of inflammation in fat and muscle [is also acting to] prevent insulin from disposing blood glucose into tissues that require glucose.”
Formerly known as juvenile-onset or insulin-dependent diabetes, Type 1 diabetes develops when the body’s immune cells attack and destroy its own pancreatic beta cells. Without beta cells, the body is unable to produce insulin, a hormone needed to convert glucose into energy. To prevent the development of serious complications, more than 21 million individuals with Type 1 diabetes – primarily children and young adults – must receive as many as three injections of insulin each day.
Previous attempts to treat existing Type 1 diabetes were primarily focused on restoring immune tolerance, which in healthy individuals is achieved when immune system cells “turn off” so as not to overreact and attack one’s own cells. In individuals with Type 1 diabetes, the process of immune tolerance fails to work properly, thereby permitting the self-destruction of the body’s beta cells.
But lead author Maria Koulmanda, MSc, PhD, director of Non-Human Primate Research in BIDMC’s Transplantation Research Center, wondered if there might also be a role for inflammation in the disease process.
“We knew that in cases of type 2 [non-insulin dependent] diabetes, a form of inflammation in muscle and fat prevents insulin from triggering the transfer of glucose from the blood into important insulin-sensitive tissues,” explains Koulmanda, who is also Assistant Professor of Surgery at HMS. “We thought that in addition to autoimmune destruction of insulin-producing cells, there might also be inflammation-induced insulin resistance [in type 1 diabetes.]”
To test this hypothesis, the authors administered a “cocktail” of three separate agents (rapamycin plus agonist IL-2- and antagonist-type, mutant IL-15-related Ig fusion proteins) in a NOD (non-obese diabetes) mouse model of type 1 diabetes. The therapy regimen, which included two novel immunoglobulin-fusion proteins, was aimed at both increasing tolerance and decreasing inflammation.
As predicted, following two to four weeks of treatment, the mice that had received the triple therapy maintained normal levels of blood sugar. In contrast, the control group of diabetic mice did not survive, despite receiving insulin.
The authors then conducted a molecular analysis which confirmed that the treatment had eliminated insulin resistance and relieved inflammation in the animals’ fat and muscle tissues.
“Although the treatment halted the progressive loss of insulin producing cells, the restoration of normal blood glucose levels actually was the result of inflammation being ablated in fat and muscle cells,” explains Strom. “By blocking the inflammation, we were able to restore the animals’ abilities to respond to insulin.”
“Our findings are very promising,” adds Koulmanda. “Type 1 diabetes is a serious disease requiring that children and young adults take insulin two to three times a day.”
And, she adds, despite this arduous therapy, insulin treatment does not prevent the occurrence of serious late-arising complications, including kidney failure, blindness and widespread cardiovascular disease.
“In clinical practice, it is not currently possible to identify when and if an individual will develop type 1 diabetes,” says Koulmanda. “Therefore, it is urgent to identify treatments that can restore normal blood glucose levels in patients with new-onset diabetes before insulin-producing cells are totally destroyed. We hope that our findings offer new hope in the long search for a cure of type 1 diabetes.”
Bonnie Prescott | EurekAlert!
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute
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...
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...
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,...
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...
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...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy