Study describes pharmacological action of TZDs directly on pancreas

Published on February 18, 2013 at 6:19 AM · No Comments

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 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 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 pancreas?

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