Diabetes Mellitus (DM) is a chronic metabolic disease characterized by an abnormal increase in blood sugar and needing continuous care. The World Health Organization (WHO) estimates that 6% of world population is a carrier of DM. The prevalence of disease increases with age in both sexes, and the estimated risk of DM throughout life is 30 to 40%, and is associated with the development of lesions in the pancreas and in the long term, to an increased risk of ophthalmological, renal, cardiac, vascular or neuropathic complications. 

Depending on its cause, DM can be classified as type 1 diabetes (T1DM, autoimmune and characterized by the death of pancreatic β cells, specifically of the pancreatic islet, responsible for insulin production) and type 2 diabetes (T2DM), also known by late diabetes and which begins with insulin resistance, a condition in which cells fail to respond to insulin properly. As the disease progresses a lack of insulin production may also develop. Also, in this type of diabetes, there is aggregation of Islet Amyloid PoliPeptides (IAPP) considered as a critical pathological process associated with the death of pancreatic β cells, a situation that also occurs in patients undergoing transplantation of the pancreas.

High levels of IAPP have also been found in newly diagnosed patients with T1DM suggesting the toxicity of IAPP also as a pathological factor which accelerates the initial disease progression.

"The current therapies for the treatment of DM focus mainly on the control of blood sugar level by insulin administration. Although not a permanent cure, these treatments if followed regularly provide health and quality of life for the patient. Few efforts have been made to develop a more targeted strategy to prevent the death of pancreatic β cells, and this is what we are aiming at in this project" says Regina Menezes, researcher at IBET and ITQB-NOVA and one of the project leaders.

According to the researcher, this project will not only allow to provide clinical support for the pathological role of aggregation of IAPP in the initial progression of T1DM but also in the development of T2DM and in the failure of pancreatic transplantation in patients with T2DM. Moreover, it will unravel the pathways associated with toxicity of IAPP in order to identify cellular targets for the development of therapeutic alternatives, which may involve molecules similar to polyphenolic metabolites. 

"We have been investigating the role of polyphenolic compounds (such as those existing in blueberries and raspberries) and more specifically the metabolites generated after ingestion and their effect on the prevention of IAPP amyloid fibrils formation and their toxicity and the results are very encouraging" says Cláudia Santos, coordinator of the Molecular Nutrition and Health laboratory at IBET and ITQB-NOVA.

As a final goal, this project aims to explore the versatility of cellular models of aggregation of IAPP (in yeast, cell lines and primary pancreatic β cells) and animal models alongside with clinical studies, in order to increase the current knowledge on the role of IAPP in the development and progression of diabetes and to convert this knowledge into new therapeutic strategies and innovative medicines.

Therapeutics4DM: Elucidação do papel do Péptido Amiloide dos Ilhéus em Diabetes Mellitus: abrindo novos caminhos para a intervenção terapêutica
Project Leaders: Regina Menezes (iBET and ITQB-NOVA); Rogério Ribeiro (CEDOC and APDP)