Molecular mechanisms involved in pancreatic beta cell dysfunction and death in Diabetes Mellitus: strategies for the inhibition of these processes and restoration of the insular mass

• Grant number: 21/04664-7
• Support Opportunities: Research Projects - Thematic Grants
• Start date: February 01, 2023
• End date: January 31, 2028
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Antonio Carlos Boschiero
• Grantee: Antonio Carlos Boschiero
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Claudio Cesar Zoppi ; Emerielle Cristine Vanzela ; Gustavo Jorge dos Santos ; Helena Cristina de Lima Barbosa ; Marcelo Alves da Silva Mori ; Maria Lucia Bonfleur ; Mirian Ayumi Kurauti ; Sandra Lucinei Balbo
• Associated research grant(s): 23/13857-9 - INVOLVEMENT OF THE VAGUS NERVE AND HYPOTHALAMIC REGULATORS IN ENERGY HOMEOSTASIS IN OBESE MICE, AV.BR
• Associated scholarship(s): 24/20739-5 - Training in laboratory techniques for research in endocrine pancreatic metabolism., BP.TT; 24/04870-4 - Effect of intracerebroventricular administration of irisin on hippocampal inflammation in obese C57BL/6Unib mice, BP.IC; 24/04650-4 - Analysis of the effects of chronic central treatment with irisin on hepatic lipid metabolism in mice subjected to the diet-induced obesity model, BP.IC; + associated scholarships 24/04705-3 - Effects of endurance exercise on plasma GDF-15 levels and the crosstalk between skeletal muscle and endocrine pancreas, BP.PD; 24/05353-3 - Training in Laboratory Techniques for Endocrine Pancreas Metabolism Research, BP.TT; 22/15059-0 - Identification of the molecules mediating the effects of resistance exercise training on pancreatic beta cell function and survival, BP.PD - associated scholarships

Abstract

Diabetes Mellitus is a chronic metabolic syndrome that affects hundreds of millions of people, and is the direct cause of death for over a million people every year. Severe chronic complications associated to it are the main cause of blindness and visual dysfunctions, limb amputation, kidney failure, neuropathies, and cardiovascular diseases. Maintaining glicemic homeostasis is crucial to avoid deaths and patient complications, including those related to other non-chronic diseases, such as Covid-19. The two main forms of the disease are type 1 Diabetes (DM1) that corresponds to 5-15%, and type 2 (DM2) that corresponds to 80-85% of all cases of Diabetes Mellitus. In DM2, the onset of the disease involves a genetic pre-disposition, associated with multiple environmental factors, being obesity one of the major factors that predispose the individual in developing this type of Diabetes. As for DM1, the pathogenesis is not yet fully understood, but it is known that the reduction of beta-cell mass occurs due the contact with cells from the immune system, associated with pro-inflammatory mediators such as the cytokines, leading to apoptosis. The reduction of insulin production and secretion, provoked by a progressive loss of function and mass of the beta cells, is a common characteristic for both DM1 and DM2. In this project, we will investigate interventions that could ameliorate DM, focusing on beta-cells, by studying molecular mechanisms that participate in their maturation, function, and mass, as well as in other tissues involved in the glicemic homeostasis regulation, such as skeletal muscle, liver, adipose tissue, and neural system. Also, we will focus on the participation of the vagus nerve and hypothalamic regulators in the energetic homeostasis of obese mouse and their actions upon the physiopathology of pancreatic islets. In addition, we will expand our investigation to isolated human islets, obtained from pancreas donated by patients, as well as in undifferentiated hPSC-beta cells (an area poorly developed in Brazil). Finally, we would like to state that our group possesses all the necessary structure and collaborators that allow us to propose this advancement. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BALBO, SANDRA LUCINEI; SOARES, GABRIELA MOREIRA; MORARI, JOSEANE; FELISBERTO JR, ANTONIO MACHADO; VETTORAZZI, JEAN FRANCIESCO; BRONCZEK, GABRIELA ALVES; BONFLEUR, MARIA LUCIA; CARNEIRO, EVERARDO MAGALHAES; BOSCHERO, ANTONIO CARLOS; VELLOSO, LICIO AUGUSTO. Impact of Sleeve Gastrectomy on Body Weight and Food Intake Regulation in Diet-Induced Obese Mice. CURRENT ISSUES IN MOLECULAR BIOLOGY, v. 46, n. 11, p. 8-pg., 2024-11-01. (13/07607-8, 15/12611-0, 21/04664-7, 19/00728-0)