Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Joslin study indicates insulin receptors play a critical role in promoting islet growth

04.04.2007
Findings may lead to treatments that enhance beta cell growth

A new Joslin-led study has identified the insulin receptor as an important protein that promotes islet cell growth in mice whose bodies are unable to use insulin properly, or are insulin resistant, a precursor to type 2 diabetes.

Since the body's natural response to insulin resistance is to increase insulin secretion from the pancreas and grow more islet cells, also known as beta cells, harnessing this growth response could lead to new treatments for type 2 diabetes. The study appears in the early online edition of this week's Proceedings of the National Academy of Sciences.

"The failure to grow more functional beta cells (also called compensatory islet cell growth response) leads to overt diabetes," said Rohit N. Kulkarni, M.D., Ph.D., Investigator at Joslin Diabetes Center and Assistant Professor of Medicine at Harvard Medical School, who led the study. "If we can identify the key signaling proteins critical for the islet cell growth response, we can develop potential therapeutic targets to enhance the growth of beta cells."

There are two proteins that mediate the effects of growth factors in beta cells, the insulin-producing cells in the pancreas: insulin receptor, a protein that mediates the action of insulin, and IGF-1 receptor, another protein that closely resembles the insulin receptor and mediates the action of insulin-like-growth factor (IGF-I), a hormone and growth factor. These two receptors have been a major focus of research studies by Dr. Kulkarni and others at Joslin Diabetes Center who want to better understand beta cell growth and functioning so that these essential cells can be increased in people with diabetes.

In type 2 diabetes, the body doesn't produce enough insulin and/or is unable to use insulin properly (insulin resistance). This form of diabetes usually occurs in people who are over 40, overweight, and have a family history of diabetes, although today it is increasingly occurring in younger people, including adolescents. For reasons that are still unknown, islet cells malfunction in people with type 2 diabetes and their bodies are unable to compensate. By investigating the cellular mechanisms that affect islet cell growth and development, Joslin researchers hope to improve the process to better treat type 2 diabetes, the most common form of diabetes.

This study investigated whether insulin receptors in the beta cell play a key role in promoting their growth as a response to overcome insulin resistance. A state of transient insulin resistance occurs naturally during pregnancy and puberty, but without causing diabetes in most people because the beta cells are able to grow and secrete more insulin to easily overcome the insulin resistance. It is when the beta cells fail to grow and secrete more insulin in these states that overt diabetes develops.

Two mouse models were used in the study. In the first model, an insulin-resistant mouse was crossed with a mouse lacking insulin receptors in the beta cell. The resulting offspring had insulin resistance with no receptors in the beta cell. In spite of their insulin resistance, the mice didn't show an appropriate growth response in the islets because the beta cells lacked insulin receptors. "This provided genetic evidence that insulin receptors are important for the islet cell growth response to insulin resistance," said Dr. Kulkarni.

In the second part of the study, researchers examined the role of the two related receptors--insulin and IGF-1. They used two mouse models--beta-cell-specific insulin receptor knockouts (beta-IRKO), which lack insulin receptors in beta cells, and IGF-1 receptor knockout (beta-IGF1RKO), which lack IGF-1 receptors in beta cells. Both these mouse models were then compared to a control group of mice normally expressing both insulin and IGF-1 receptors in their beta cells. All three groups were placed on a high-fat diet to induce insulin resistance.

The researchers assessed the beta cell growth response in the pancreas: the beta-IRKO mice failed to show the growth of islet cells while the control and beta-IGF1RKO mice did exhibit this growth response. "The results clearly showed that it is the insulin receptor -- not the IGF-1 receptor -- that is critical for the islet cell growth response to insulin resistance," said Dr. Kulkarni.

Joslin researchers are working on a follow up study that aims to identify the proteins that control the signaling pathway. "We are excited about the possibilities to make further progress in this area," Kulkarni said.

Jenny Eriksen | EurekAlert!
Further information:
http://www.joslin.harvard.edu

More articles from Health and Medicine:

nachricht Vanishing capillaries
23.03.2017 | Technische Universität München

nachricht How prenatal maternal infections may affect genetic factors in Autism spectrum disorder
22.03.2017 | University of California - San Diego

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: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Inactivate vaccines faster and more effectively using electron beams

23.03.2017 | Life Sciences

New study maps space dust in 3-D

23.03.2017 | Physics and Astronomy

Tracing aromatic molecules in the early universe

23.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>