Metabolomic study of the biochemical mechanism of action of 2-aminoadipate in type 2 diabetes mellitus development

• Grant number: 13/06729-2
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 01, 2013
• End date: October 31, 2014
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Ana Carolina de Mattos Zeri
• Grantee: Marcos Rodrigo Alborghetti
• Supervisor: Robert E. Gerszten
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Institution abroad: Massachusetts General Hospital, United States
• Associated to the scholarship: 11/06441-3 - Prospective analysis of the blood serum metabolome of patients undergoing bone marrow transplantation in the study of the GVHD (Graft-Versus-Host Disease), BP.PD

Abstract

The applicant's mentor, Dr. Gerszten, and collaborators have identified and validated amino acid and lipid profiles of individuals destined to develop overt Diabetes Mellitus (DM) and atherosclerosis. In new unpublished work, the Gerszten laboratory has performed an analysis of "intermediate" metabolites using a recently-developed method for profiling organic acids, purines and pyrimidines and other small molecules. In the Framingham Heart Study (FHS), the intermediate metabolite most strongly associated with incident DM was 2-aminoadipic acid (2-AAA). These discovery findings in human populations demonstrate the feasibility of applying metabolite profiling techniques to large populations. The findings, however, are merely associations that generate hypotheses for further testing in appropriate model systems. Thus, the present proposal will specifically evaluate the potential functional role of a key metabolite identified in Dr. Gerszten's most recent study, 2-AAA. Based on preliminary studies in the laboratory, it is believed that 2-AAA plans a counter-regulatory role (like insulin) in early diabetes. Mice will be fed either a standard and hypercaloric diet, with or without 2-AAA supplementation. Effects on diabetic parameters will be evaluated intraperitoneal glucose and insulin tolerance tests. It is expected a better understanding about the mechanisms of action of this molecule in normal and pre-diabetic state and its involvement in glucose metabolism and development of type 2 diabetes mellitus. (AU)