Cristina Quesada-Candela1, Eva Tudurí1, Laura Marroquí1, Paloma Alonso-Magdalena1, Ivan Quesada2, Ángel Nadal3. 1. Instituto de Biología Molecular y Celular (IBMC), Universitas Miguel Hernández, 03202 Elche, Spain; Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández, 03202 Elche, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Spain. 2. Instituto de Biología Molecular y Celular (IBMC), Universitas Miguel Hernández, 03202 Elche, Spain; Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández, 03202 Elche, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Spain. Electronic address: ivanq@umh.es. 3. Instituto de Biología Molecular y Celular (IBMC), Universitas Miguel Hernández, 03202 Elche, Spain; Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE), Universitas Miguel Hernández, 03202 Elche, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Spain. Electronic address: nadal@umh.es.
Abstract
BACKGROUND: Pregnancy represents a major metabolic challenge for the mother, and involves a compensatory response of the pancreatic beta-cell to maintain normoglycemia. However, although pancreatic alpha-cells play a key role in glucose homeostasis and seem to be involved in gestational diabetes, there is no information about their potential adaptations or changes during pregnancy. MATERIAL AND METHODS: Non-pregnant (controls) and pregnant C57BL/6 mice at gestational day 18.5 (G18.5) and their isolated pancreatic islets were used for in vivo and ex vivo studies, respectively. The effect of pregnancy hormones was tested in glucagon-secreting α-TC1.9 cells. Immunohistochemical analysis was performed in pancreatic slices. Glucagon gene expression was monitored by RT-qPCR. Glucagon secretion and plasma hormones were measured by ELISA. RESULTS: Pregnant mice on G18.5 exhibited alpha-cell hypertrophy as well as augmented alpha-cell area and mass. This alpha-cell mass expansion was mainly due to increased proliferation. No changes in alpha-cell apoptosis, ductal neogenesis, or alpha-to-beta transdifferentiation were found compared with controls. Pregnant mice on G18.5 exhibited hypoglucagonemia. Additionally, in vitro glucagon secretion at low glucose levels was decreased in isolated islets from pregnant animals. Glucagon content was also reduced. Experiments in α-TC1.9 cells indicated that, unlike estradiol and progesterone, placental lactogens and prolactin stimulated alpha-cell proliferation. Placental lactogens, prolactin and estradiol also inhibited glucagon release from α-TC1.9 cells at low glucose levels. CONCLUSIONS: The pancreatic alpha-cell in mice undergoes several morphofunctional changes during late pregnancy, which may contribute to proper glucose homeostasis. Gestational hormones are likely involved in these processes.
BACKGROUND: Pregnancy represents a major metabolic challenge for the mother, and involves a compensatory response of the pancreatic beta-cell to maintain normoglycemia. However, although pancreatic alpha-cells play a key role in glucose homeostasis and seem to be involved in gestational diabetes, there is no information about their potential adaptations or changes during pregnancy. MATERIAL AND METHODS: Non-pregnant (controls) and pregnant C57BL/6 mice at gestational day 18.5 (G18.5) and their isolated pancreatic islets were used for in vivo and ex vivo studies, respectively. The effect of pregnancy hormones was tested in glucagon-secreting α-TC1.9 cells. Immunohistochemical analysis was performed in pancreatic slices. Glucagon gene expression was monitored by RT-qPCR. Glucagon secretion and plasma hormones were measured by ELISA. RESULTS: Pregnant mice on G18.5 exhibited alpha-cell hypertrophy as well as augmented alpha-cell area and mass. This alpha-cell mass expansion was mainly due to increased proliferation. No changes in alpha-cell apoptosis, ductal neogenesis, or alpha-to-beta transdifferentiation were found compared with controls. Pregnant mice on G18.5 exhibited hypoglucagonemia. Additionally, in vitro glucagon secretion at low glucose levels was decreased in isolated islets from pregnant animals. Glucagon content was also reduced. Experiments in α-TC1.9 cells indicated that, unlike estradiol and progesterone, placental lactogens and prolactin stimulated alpha-cell proliferation. Placental lactogens, prolactin and estradiol also inhibited glucagon release from α-TC1.9 cells at low glucose levels. CONCLUSIONS: The pancreatic alpha-cell in mice undergoes several morphofunctional changes during late pregnancy, which may contribute to proper glucose homeostasis. Gestational hormones are likely involved in these processes.