Featured Research

from universities, journals, and other organizations

New advances in the molecular study of diabetes

Date:
February 18, 2013
Source:
Universidad de Barcelona
Summary:
A new study describes for the first time the pharmacological action of thiazolidinediones (TZDs) -- anti-diabetic drugs -- directly on the pancreas, the organ which produces insulin.

A scientific study published on the journal Diabetes, edited by the American Diabetes Association, describes for the first time the pharmacological action of thiazolidinediones (TZDs) -- anti-diabetic drugs -- directly on the pancreas, the organ which produces insulin.

The research, carried out with laboratory animal models, is led by the professor Carme Caelles, from the Cell Signaling Research Group from the Department of Biochemistry and Molecular Biology (Faculty of Pharmacy), together with the team of Dr Ramon Gomis, from the Hospital Clínic of Barcelona -- IDIBAPS.

Insulin is the main hormone which regulates blood glucose levels. When the pancreas does not produce enough insulin, type 1diabetes takes place, which requires a daily administration of insulin. On the contrary, type 2 diabetes is caused by a problem in the way your body uses insulin (resistance to his hormone) and is associated with overweight and physical inactivity.

Type 2 diabetes: a public health issue

The article published on Diabetes analyses type 2 diabetes: the most common form of diabetes (85-90 % of diabetics). Often, people with type 2 diabetes have no symptoms at first, but it end up producing hyperglycemia due to insulin resistance. In other words, in this type of diabetes, tissues do not answer to this hormone signal and, consequently, cells are not able to absorb insulin (the main body source of energy). So, pancreatic β-cells produce extra insulin which results in pancreatic hyperplasia.

In the pharmacological field, type 2 diabetes can be treated with some drugs such as sulfonylureas, which increase insulin production and facilitate glucose absorption to cell metabolism (anti-hyperglycemic action). Other drugs, for example metformin, can also help as they limit the glucose synthesis carried out by the liver.

Studying molecular signaling pathways

The work is focused on the action of thiazolidinediones (TZDs), oral anti-diabetic drugs which reduce insulin resistance and exert insulin-sensitizing action directly on tissues. According to the professor Carme Caelles, at her laboratory in the Barcelona Science Park, "the action mechanism of TZDs is not well known yet. Their receptor (the PPARγ) has been identified; but we do not know yet how they act at molecular level."

In a previous article, published on Diabetes in 2007, researchers proved that TZDs inhibit JNK kinase (c-Jun N-terminal kinase), a transducer of biochemical signals which inhibit insulin signaling and is related to insulin resistance. "Then -- add Caelles -- , we proved that the pharmacological action of TZDs includes JNK inhibition and this effect is more effective on adipose tissues, where PPARγ is mostly expressed."

Is TZDs action also effective on the pancreas?

The authors of the study have provided the first evidence of TZDs pharmacological action on pancreatic β cells -- insulin producers -- and shown new research lines on the action of these drugs to control glucose metabolism. The study generated a transgenic mouse model that allows JNK activation in tissues which has been an excellent in vivo model to prove the action mechanism of TZD drugs.

The conclusions stated that JNK activation is necessary to generate insulin resistance -- in pancreatic β-cells -- which generates a glucose intolerance phenotype in the mice experimental model. Curiously, this phenotype does not correlate with any obvious morphological or structural abnormality in the pancreas or the islets. In fact, despite previous literature, pancreatic β-cells do not die exclusively by JNK activation.

Caelles remarks that "we knew that pancreatic β-cells also have the receptor PPARγ, but now we know that TZDs have a role in central insulin resistance. All the pharmacological actions described were attributed to the receptor expression in peripheral tissues, such the adipose (peripheral insulin resistance)."

Diabetes, obesity and inflammation

Many scientific studies prove a connection among molecular signaling pathways of diabetes, obesity and inflammation. "During an inflammation process, JNK kinase is also activated," explains Caelles. "In type 2 diabetes -- he explains -- , the extra insulin demand generates a pancreatic hyperplasia which causes inflammation. Obesity is also related to a low-grade, chronic inflammatory state, this could explain its link with insulin resistance. Therefore, in obesity, adipose tissue catches cells of the immune system, and increases the levels of inflammation mediators (interleukins, etc.). As JNK kinase is active during all this process, insulin is not able to regulate glucose metabolism."

The scientific team led by Carme Caelles mainly studies the regulation mechanism of the different signaling pathways in cell processes which are fundamental for metabolism. Taking into account the last scientific results, the team is fostering new research lines with animal models to analyse the physiologic and biochemical answer of β-cells in extreme conditions (high-fat diet, peripheral insulin resistance, etc.), and to know the evolution of insulin resistance mechanism in aging.

The article published on Diabetes, which is also signed by the experts Jordi Lamuza-Masdeu and M. Isabel Arévalo (Faculty of Pharmacy), Cristina Vila (IRB Barcelona) and Albert Barberà (Hospital Clínic of Barcelona-IDIBAPS), can be read on this link.


Story Source:

The above story is based on materials provided by Universidad de Barcelona. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. Lanuza-Masdeu, M. I. Arevalo, C. Vila, A. Barbera, R. Gomis, C. Caelles. In vivo JNK activation in pancreatic  -cells leads to glucose intolerance caused by insulin resistance in pancreas. Diabetes, 2013; DOI: 10.2337/db12-1097

Cite This Page:

Universidad de Barcelona. "New advances in the molecular study of diabetes." ScienceDaily. ScienceDaily, 18 February 2013. <www.sciencedaily.com/releases/2013/02/130218092503.htm>.
Universidad de Barcelona. (2013, February 18). New advances in the molecular study of diabetes. ScienceDaily. Retrieved October 1, 2014 from www.sciencedaily.com/releases/2013/02/130218092503.htm
Universidad de Barcelona. "New advances in the molecular study of diabetes." ScienceDaily. www.sciencedaily.com/releases/2013/02/130218092503.htm (accessed October 1, 2014).

Share This



More Health & Medicine News

Wednesday, October 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Cases Keep Coming for Monrovia's Island Hospital

Ebola Cases Keep Coming for Monrovia's Island Hospital

AFP (Oct. 1, 2014) — A look inside Monrovia's Island Hospital, a key treatment centre in the fight against Ebola in Liberia's capital city. Duration: 00:34 Video provided by AFP
Powered by NewsLook.com
Ebola Puts Stress on Liberian Health Workers

Ebola Puts Stress on Liberian Health Workers

AP (Oct. 1, 2014) — The Ebola outbreak is putting stress on first responders in Liberia. Ambulance drivers say they are struggling with chronic shortages of safety equipment and patients who don't want to go to the hospital. (Oct. 1) Video provided by AP
Powered by NewsLook.com
Doctors Reassure Public Ebola Patient Won't Cause Outbreak

Doctors Reassure Public Ebola Patient Won't Cause Outbreak

Newsy (Sep. 30, 2014) — After the announcement that the first U.S. patient had been diagnosed with Ebola, doctors were quick to say a U.S. outbreak is highly unlikely. Video provided by Newsy
Powered by NewsLook.com
TX Hospital Confirms Patient Admitted With Ebola

TX Hospital Confirms Patient Admitted With Ebola

AP (Sep. 30, 2014) — Medical officials from Texas Health Presbyterian Hospital confirm they are treating a patient with the Ebola virus, the first case found in the US. (Sept. 30 Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins