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| Author(s): |
Cristiane dos Santos
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2021-06-22 |
| Examining board members: |
Antonio Carlos Boschero;
Helena Cristina Barbosa Sampaio;
Silvana Bordin;
Marcelo Alberto Torsoni
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| Advisor: | Antonio Carlos Boschero; Alex Rafacho |
| Abstract | |
The pancreatic islets exhibit cellular plasticity that includes the capability to recover beta-cell mass after a significant loss (e.g., induced by streptozotocin (STZ) in neonatal rodents). The glucocorticoid (GC) excess during late pregnancy, resulting from treatment with synthetic GC or high endogenous levels, increases the risk of metabolic dysfunction in offspring, but its effect on beta-cell recovery is unknown. To investigate these effects, pregnant mice were administered vehicle or dexamethasone (DEX) in the third period of gestation. Pups on postnatal day (PN) 6 were treated with STZ or vehicle solution, resulting in four experimental groups: CC, CS, DC and DS. Functional and molecular analyses were performed in male offspring on PN25 and PN225. Prenatal DEX treatment resulted in low birthweight, a marker of fetal programming. At PN25, both the STZ-treated offspring developed hyperglycemia and lower alpha-cell mass, in parallel with higher ?-cells mass and glucose intolerance, with no impact of prenatal DEX on such parameters. These results were corroborated by the genetic expression of pancreatic hormones. At PN225, the beta-cell mass was partially reconstituted in the STZ-treated mice, but they remained glucose-intolerant, irrespective to be insulin sensitive. Prenatal DEX exposure predisposed adult offspring to sustained hyperglycemia and reduced islet function (lower insulin and higher glucagon response to glucose) that paralleled with an exacerbated glucose intolerance in DS mice. ?-cell-specific knockdown of the Hnf4? in mice from the DS group resulted in exacerbated glucose intolerance. We conclude that high GC exposure during the prenatal period, predisposes the offspring to a lesser ability to recover the islets’ function after a postnatal insult with STZ. This study alerts the importance of proper management of exogenous GCs during pregnancy and a healthy postnatal lifestyle since the combination of adverse factors during the prenatal and postnatal period accentuates the predisposition to metabolic disorders in adult life, such as Diabetes Mellitus (AU) | |
| FAPESP's process: | 16/23140-0 - Endocrine pancreas plasticity of mice offspring after maternal treatment with glucocorticoid during late gestation |
| Grantee: | Cristiane dos Santos |
| Support Opportunities: | Scholarships in Brazil - Doctorate |