| Summary: |
Type II diabetes is a worldwide epidemics resulting from poor lifestyle choices, including dietary habits and lack of exercise.
Evidence exists showing that life in the womb predisposes the offspring for metabolic diseases in the adult life. Mitochondria are mediators of hyperglycemia-induced fetal developmental complications. Mitochondria are present in most eukaryotic cells and vary
in number from hundreds to thousands, depending on metabolic activity of the tissue. Mitochondrial-formed ATP can be used by the cell for many functions including the maintenance of transmembrane ion gradients, protein synthesis, vesicular transport,
metabolite secretion (as insulin in pancreatic beta-cells) as well as muscle activity. Mitochondria have also an important role in calcium homeostasis, intermediate metabolism, cell death regulation and generation of oxygen free radicals. Diabetes during
pregnancy can affect fetal cellular signaling pathways, including mitochondrial bioenergetics, leading to the development of several metabolic diseases in the adulthood. Although pharmacological approaches exist to control diabetic-induced complications, a
voluntary change in lifestyle is often more effective, also sparing mother and fetus from being exposed to chemical agents.
Voluntary physical activity (VPA) during pregnancy is a powerful approach, which can be benefic for mother, fetus and later child. By using a rodent model of gestational diabetes, we intend to demonstrate for the first time that hyperglycemic pregnant mothers
subjected to VPA have offspring with a more robust mitochondrial function and demonstrating better cognitive functions when compared with offspring from sedentary pregnant mothers. For the present work, we will use the Goto-Kakizaki (GK) animal model.
The GK rat has been generated as an animal model of non-insulin-dependent diabetes mellitus. This animal is a spontaneously diabetic rat, produced by selective inbreeding of Wistar rats with the highest  |
Summary
Type II diabetes is a worldwide epidemics resulting from poor lifestyle choices, including dietary habits and lack of exercise.
Evidence exists showing that life in the womb predisposes the offspring for metabolic diseases in the adult life. Mitochondria are mediators of hyperglycemia-induced fetal developmental complications. Mitochondria are present in most eukaryotic cells and vary
in number from hundreds to thousands, depending on metabolic activity of the tissue. Mitochondrial-formed ATP can be used by the cell for many functions including the maintenance of transmembrane ion gradients, protein synthesis, vesicular transport,
metabolite secretion (as insulin in pancreatic beta-cells) as well as muscle activity. Mitochondria have also an important role in calcium homeostasis, intermediate metabolism, cell death regulation and generation of oxygen free radicals. Diabetes during
pregnancy can affect fetal cellular signaling pathways, including mitochondrial bioenergetics, leading to the development of several metabolic diseases in the adulthood. Although pharmacological approaches exist to control diabetic-induced complications, a
voluntary change in lifestyle is often more effective, also sparing mother and fetus from being exposed to chemical agents.
Voluntary physical activity (VPA) during pregnancy is a powerful approach, which can be benefic for mother, fetus and later child. By using a rodent model of gestational diabetes, we intend to demonstrate for the first time that hyperglycemic pregnant mothers
subjected to VPA have offspring with a more robust mitochondrial function and demonstrating better cognitive functions when compared with offspring from sedentary pregnant mothers. For the present work, we will use the Goto-Kakizaki (GK) animal model.
The GK rat has been generated as an animal model of non-insulin-dependent diabetes mellitus. This animal is a spontaneously diabetic rat, produced by selective inbreeding of Wistar rats with the highest glucose values during oral glucose tolerance tests. We
expect to confirm the protective effect from VPA even when both mother and father were hyperglycemic. If protection resulting from VPA is obtained, this relevant work will show that VPA contributes to protect the future offspring from the development of further
metabolic disease and will decrease the incidence of organ degeneration motivated by in utero hyperglycemic insult. From a human point of view, the impact is very high. The results can be translated into a motivational will to perform moderate exercise during
pregnancy if a diabetic condition is present. We believe that this change in paradigm will lead many health-related professionals to recommend physical activity to the diabetic mother, in case no other counter-indications exist.
The results obtained in this project will be disseminated as full length publications in high impact peer-reviewed scientific journals (e.g. Diabetes, Clinical Sciences, PNAS or others), and presented under the form of posters or short oral talks in different national
and international meetings).
The present project is a fortunate combination of six recognized scientists with very strong CVs and different backgrounds (the
Principal Investigator, António Moreno, Paulo J. Oliveira, Carlos Palmeira, Anabela Rolo, António Ascensão and José Magalhães), and
originated in two different excellent institutions, the Center for Neuroscience and Cell Biology (CNBC/UC), and the Research Centre
in Physical Activity, Health and Leisure (CIAFEL/UP). The team has extensive experience in animal models for hyper |