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 Cystic fibrosis alters the structure of mucus in airways
28.06.2017 | University of Iowa Health Care

nachricht Mice provide insight into genetics of autism spectrum disorders
28.06.2017 | University of California - Davis

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: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Supersensitive through quantum entanglement

28.06.2017 | Physics and Astronomy

X-ray photoelectron spectroscopy under real ambient pressure conditions

28.06.2017 | Physics and Astronomy

Mice provide insight into genetics of autism spectrum disorders

28.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>