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 September 17, 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 September 17, 2014).

Share This



More Health & Medicine News

Wednesday, September 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) — President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Obama Orders Military Response to Ebola

Obama Orders Military Response to Ebola

AP (Sep. 16, 2014) — Calling the Ebola outbreak in West Africa a potential threat to global security, President Barack Obama is ordering 3,000 U.S. military personnel to the stricken region amid worries that the outbreak is spiraling out of control. (Sept. 16) Video provided by AP
Powered by NewsLook.com
UN: 20,000 Could Be Infected With Ebola by Year End

UN: 20,000 Could Be Infected With Ebola by Year End

AFP (Sep. 16, 2014) — Nearly $1.0 billion dollars is needed to fight the Ebola outbreak raging in west Africa, the United Nations say, warning that 20,000 could be infected by year end. Duration: 00:40 Video provided by AFP
Powered by NewsLook.com
Obama: Ebola Outbreak Threat to Global Security

Obama: Ebola Outbreak Threat to Global Security

AP (Sep. 16, 2014) — President Obama is ordering U.S. military personnel to West Africa to deal with the Ebola outbreak, which is he calls a potential threat to global security. (Sept. 16) 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:
from the past week

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