Analysis of the indoleamine 2,3 dioxygenase enzyme role on glucagon secretion in a streptozotocin-induced Diabetes model

• Grant number: 13/25198-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2014
• End date: December 31, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Humberto Dellê
• Grantee: Yves Silva Teles Matos
• Host Institution: Universidade Nove de Julho (UNINOVE). Campus Vergueiro. São Paulo , SP, Brazil

Abstract

Diabetes Mellitus (DM) is a chronic metabolic disorder that arises due to deficiency of insulin secretion or action of this hormone, resulting in hyperglycemia. There is an imbalance in hormonal secretion by pancreatic islets (PI), where insulin deficiency leads to an increase of glucagon due to loss of inhibitory signals, which intensifies the hyperglycemia, due to the hepatic effects of glucagon. This imbalance is demonstrated in the streptozotocin-induced DM model. In previous studies, we found that peripheral cells of PI (pancreatic alpha cells) express a molecule called indoleamine 2,3 dioxygenase (IDO) and this expression increases from the administration of streptozotocin. IDO has been considered a biomodulator molecule, mainly because of the description of their roles in protecting the fetus against the maternal immune system, in action against pathogens, and modulating cell signaling. Moreover, IDO, from the degradation of tryptophan, provides NAD+ to the microenvironment where it is present. Because glucagon secretion depends on NAD+ and is increased on the streptozotocin-induced DM model, a model where IDO expression is increased in alpha cells, it is possible that the IDO plays a role in the glucagon secretion. The aim of this study is to analyze the effect of IDO inhibition in the streptozotocin-induced DM model, in order to investigate the role of IDO on glucagon secretion. In addition, verify whether PI-NAD+ levels of normal and diabetic rats are altered by IDO inhibition. Thus, we will use Wistar rats to induce DM, treated or not with IDO inhibitor (methyl tryptophan, MT), to evaluate blood glucose and weight gain of the animals for a period of 30 days, as well as the glucagon serum at the end of this period. An "in vitro" experiment will be performed by isolating PI from normal and diabetic rats, which will be submitted to the IDO inhibition in culture after challenge to glucagon secretion, being evaluated the NAD+ production in this controlled situation. (AU)