The role of prions in the control of insulin response

• Grant number: 14/50266-0
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2014
• End date: July 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Agreement: University of Melbourne
• Principal Investigator: Vilma Regina Martins
• Grantee: Vilma Regina Martins
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Associated research grant: 09/14027-2 - Mechanisms associated with the function of prion protein and its ligand STI1/Hop: therapeutic approaches, AP.TEM

Abstract

The prion protein (PrPC) plays major roles in cellular functions by binding to diverse proteins, forming multi-protein complexes and organizing signaling platforms. These protein complexes need to be better evaluated at the molecular and cellular level in order to understand how PrPC associations trigger different cellular signals. An important role of PrPc regards the modulation of insulin response. In mice, increased PrPC expression enhances insulin response and reduces the chances of developing insulin intolerance even under high-fat diet consumption. On the other hand, PrPC knockout mice present insulin intolerance and increased body weight, much like what is observed in metabolic syndrome patients. This phenotype could be associated to a failure in the translocation of the GLUT4 glucose transporter to the plasma membrane. Data from the literature shows that mice presenting prion diseases display hyperinsulinemia with hyperglycemia, consistent with an anabolic syndrome. However the molecular mechanisms of this phenotype were not explored. To establish if prion infection also modulates insulin response, we initiated a collaboration with Dr. Andrew Hill at the University of Melbourne. Dr. Hill's research focuses in molecular and cell biology of Prion and Alzheimer's diseases and his team has a large expertise in prion models of infection. The knowledge of PrPC functions in insulin response may lead to the development of therapeutic approaches for prion diseases or metabolic syndrome and type II diabetes. (AU)