“The extremely positive worldwide scientific impact of this work constantly reminds me of the size of our responsibilities and how much society expects from us,” says Dr. Natália Tobar Toledo Prudente da Silva, biomedical scientist and associate researcher at CEPID CancerThera, when asked about the importance of receiving the Unicamp 2024 Outstanding Thesis Award in the category of Biological and Health Sciences. The award was granted for the results of her doctoral research entitled “Pharmacological effects of metformin on intestinal glucose uptake and induction of gut-liver crosstalk in the control of hepatic gluconeogenesis.”
The award ceremony took place on August 12, 2024, in the Grand Hall of the University Council of the University of Campinas (Unicamp). “I received the news of this award with great emotion and joy. It was the result of 10 years of hard work filled with immense challenges, and it only came to fruition so successfully because many highly qualified professionals were involved and dedicated themselves wholeheartedly,” says Tobar.
Among her main collaborators, the researcher highlights Prof. Dr. Mario José Abdalla Saad, her advisor, and teams from various Unicamp units, such as the Nuclear Medicine Service of the Clinics Hospital, the Institute of Biology, the Institute of Chemistry, the Faculty of Medical Sciences, the Center for Biomedical Engineering, and the Faculty of Applied Sciences. She also collaborated with professionals from external institutions, including the Department of Physical Education at São Paulo State University, the Institute of Biomedical Sciences at the University of São Paulo, the Butantan Institute, and the National Center for Research in Energy and Materials.
The study was funded by the National Institute of Science and Technology of Obesity and Diabetes, the National Council for Scientific and Technological Development, and the São Paulo Research Foundation (FAPESP).
Scientific maturity
The researcher believes that her experience in conducting the study will contribute to her work at CancerThera, a multidisciplinary research center that involves translational flow between basic, preclinical, and clinical research, with professionals from various fields of knowledge working together to advance theranostics in cancer. “All these years of dedication have mainly taught me resilience, the value of each professional’s effort and support, discipline, and the ability to develop a systemic and critical vision of everything at hand to make the most of it,” emphasizes Tobar.
She also states that carrying out the study for so long allowed her to mature her understanding of what it means to conduct research, which for her “goes beyond the scientific content itself and should extend beyond each new bench experiment, reaching those who truly need to benefit from this knowledge, which is society.” She adds, “All of this prepared me to join a project so diverse in its themes and so richly multidisciplinary in its team of scientists, equipping me for research and therapy management and student mentoring, which are the roles I currently have at CancerThera.”
respectively the Rector and the Vice-Rector for Graduate Studies at Unicamp | Photo: Antoninho Perri (Portal Unicamp).
Dr. Heloísa Assalin; Ms. Dioze Guadagnini; and Dr. Andrey Santos, collaborators and co-authors of the study | Photo: João Marques (PRP/Unicamp).
What is the awarded study about?
For over 60 years, metformin has been the most recommended and used drug in the treatment of type 2 diabetes. Until the study conducted by Tobar and Saad, it was believed that the liver was the first and main site of metformin’s action to block glucose production, particularly during fasting.
However, the researchers found that metformin induces reverse glucose uptake in the intestine, removing glucose from the bloodstream. In the intestine, the drug stimulates the reappearance of a glucose transporter known as GLUT-1 — typically only found in the intestines of fetuses and deactivated after birth. In addition to GLUT-1, metformin also activates another glucose transporter, GLUT-2.
The drug thus regulates the activity of both transporters in response to varying blood glucose levels: when glucose is high, GLUT-2 comes into action; when it is low, GLUT-1 is the protagonist. Through interaction — a kind of “conversation” — between metabolites resulting from the action of GLUT-1 and GLUT-2, the intestine signals to the liver whether or not it should reduce glucose production. Therefore, it is the intestine that ultimately determines metformin’s final effect.
This mechanism, uncovered by the researchers, opens new perspectives for further studies on type 2 diabetes treatment and reinforces the prescription of metformin as the first-choice drug for patients with the disease.
The results of Tobar’s thesis were also published as an article in The Proceedings of the National Academy of Sciences (PNAS), entitled “Metformin acts in the gut and induces gut-liver crosstalk.” The coauthors are: Natália Tobar Toledo Prudente da Silva; Mario Saad; Guilherme Z. Rocha; Andrey Santos; Dioze Guadagnini; Heloísa B. Assalin; Juliana A. Camargo; Any E. S. S. Gonçalves; Flávia R. Pallis; Alexandre G. Oliveira; Silvana A. Rocco; Raphael M. Neto; Irene Layanae de Sousa; Marcos R. Alborghetti; Maurício L. Sforça; Patrícia B. Rodrigues; Raíssa G. Ludwig; Emerielle C. Vanzela; Sérgio Q. Brunetto; Patrícia A. Boer; José A. Ro. Gontijo; Bruno Geloneze; Carla E. O. Carvalho; Patrícia O. Prada; Franco Folli; Rui Curi; Marcelo A. Mori; Marco A.R. Vinolo; Celso D. Ramos; Kleber G. Franchini; and Cláudio F. Tormena.
“I feel honored by this recognition and, once again, motivated to dedicate myself even more to developing research with significant potential impact in scientific, academic, and social spheres, such as those we are conducting at CEPID CancerThera,” says Dr. Natália Tobar, associate researcher at our research center.
Watch the video of the award ceremony
Text: Romulo Santana Osthues; with information by Camila Delmondes
