Molecular mechanisms involved in pancreatic beta cell disfunction and dead in diabetes mellitus: strategies for the inhibition of these processes and restoration of the insular mass

Abstract

Diabetes mellitus (DM) is a syndrome that affects 380 million people in the world. This syndrome may cause chronic and severe health problems, increasing morbidity and mortality. Among these complications, visual defects and blindness, limb amputation, renal failure, neuropathies and cardiovascular diseases are the most frequent. The two most important forms of diabetes are DM1 (10 - 15%) and DM2 (80 - 85%). The development of the disease depends on the combination of genetic predisposition and environmental factors. Reduction of insulin production due to the loss of function, dedifferentiation, and increase in the apoptosis of beta cells, not compensated by regeneration, is a common characteristic for DM1 and DM2. In the DM1, the reduction of beta cell mass is due to their contact with immune cells and the release of proinflammatory mediators such as cytokines, leading to apoptosis. Inadequate formation of pancreatic islets, during perinatal life, as well as malnourishment, obesity, dyslipidemia, and aging contribute to the malfunctioning of the endocrine pancreas, provoking DM2. During the different periods of life, the adaptations of the endocrine pancreas are under the control of several hormones, chemical molecules, and neuronal signals, generated in the own pancreas or in other tissues. In this project, we will continue to study the molecular mechanisms that induce positive or negative modifications in beta cells, in association with the control of glucose homeostasis. We will focus our attention on substances coming from the own islets or from other tissues (cross talk), particularly during physical exercise and dyslipidemia. (AU)