The study helps in the understanding of why those with diabetes have high blood glucose levels and could lead to development of a drug aimed at targeting glucagon levels.
"This is a very important finding because until now scientists have only speculated that insulin may be involved in keeping glucagon levels in check," said Rohit N. Kulkarni, M.D., Ph.D., Principal Investigator in the Joslin Section on Cellular and Molecular Physiology and senior author of the study published today in the April issue of Cell Metabolism.
Produced by the alpha cells in the pancreas, glucagon acts on the liver to help raise blood glucose when it becomes low. It has the opposite effect on the liver as insulin, which is released from pancreatic beta cells to lower blood glucose when it is high. In a healthy individual, the two counter each other to keep blood glucose levels balanced. In individuals with long-standing type 1 or type 2 diabetes, inappropriate glucagon secretion can increase the chances of hypoglycemia (low blood glucose levels) and can interfere with insulin therapy.
The finding suggests that for people with either type 1 or type 2 diabetes, a therapeutic approach could be developed to target insulin receptors or proteins in alpha cells in order to suppress glucagon secretion.
In addition, the research may also help in the understanding of why patients with type 1 diabetes in particular, who are required to inject insulin on a regular basis, are at risk for hypoglycemia. It was thought that this increased risk was linked in some way to insulin receptors in the alpha cells, an idea that today's study suggests is in fact the case, Dr. Kulkarni explained.
"This gives us some insight into the cause of hypoglycemia, the most common complication in patients with type 1 diabetes," he said. "Injecting insulin leads to a decrease in blood glucose. If it starts to go too low, glucagon normally kicks in to prevent hypoglycemia. But, what happens in diabetes is the alpha cells become desensitized by repeated insulin injections over many years and they start to behave abnormally. We believe this is linked to insulin receptor function."
In the study, Dr. Kulkarni and his team created a genetically engineered mouse model in which pancreatic alpha cells – those that secrete glucagon – were modified so that they did not contain insulin receptors. The idea was to explore the role of insulin in regulating glucagon secretion.
The modified mice exhibited elevated glucagon levels and also showed impaired glucose tolerance, as is seen in diabetes.
"This is the first genetic model wherein we provide definitive proof that insulin is able to suppress glucagon in mammals," Dr. Kulkarni said. "The next step is to identify the specific proteins in alpha cells that could be targeted to suppress glucagon secretion."
The paper concludes that the findings indicate there is a significant role for insulin signaling in the regulation of alpha cell functioning in both normal and hypoglycemic conditions and provide direct genetic evidence for a key role for insulin receptors in the modulation of pancreatic alpha cell function.
The study was funded in part by the American Diabetes Association, the Swiss National Science Foundation, the National Institutes of Health and the European Union.
Also contributing to the research were Dan Kawamori, Amarnath J. Kurpad, Jiang Hu, Chong Wee Liew and Judy L. Shih, all of Joslin; Eric L. Ford and Kenneth S. Polonsky, both of Washington University School of Medicine; Pedro L. Herrera, University of Geneva Medical School; and Owen P. McGuinness, Vanderbilt University School of Medicine.
About Joslin Diabetes Center
Joslin Diabetes Center is the world's preeminent diabetes research and clinical care organization. Joslin is dedicated to ensuring people with diabetes live long, healthy lives and offers real hope and progress toward diabetes prevention and a cure for the disease. Founded in 1898 by Elliott P. Joslin, M.D., Joslin is an independent nonprofit institution affiliated with Harvard Medical School. For more information about Joslin, call 1-800-JOSLIN-1 or visit www.joslin.org.
Further reports about: > Cell Metabolism > Diabetes > blood glucose > blood glucose level > carbohydrate metabolism > glucagon levels > glucose levels > glucose tolerance > hypoglycemia > inappropriate glucagon secretion > insulin receptor function > insulin therapy > low blood glucose levels > pancreatic alpha cell function > pancreatic beta cells > type 1 diabetes > type 2 diabetes
New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)
Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
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...
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...
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...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences