Insulin and glucose responses to hypoxia in male and female neonatal rats: Effects of the androgen receptor antagonist flutamide
| Autor: | Hershel Raff, Ashley L. Gehrand, Minhal Gardezi, Christine Huynh, Maya Guenther, Santiago Rolon, Jonathan Phillips |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Physiology medicine.medical_treatment 030204 cardiovascular system & hematology Flutamide Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Insulin resistance Pregnancy newborn insulin resistance Physiology (medical) Internal medicine Androgen Receptor Antagonists medicine Animals Insulin Androgen receptor antagonist Endocrine system Hypoxia Testosterone Original Research HOMA‐IR business.industry Hypoxia (medical) medicine.disease Rats Androgen receptor Disease Models Animal Glucose Endocrinology Animals Newborn chemistry Receptors Androgen sexual dimorphism Female medicine.symptom business oxygen 030217 neurology & neurosurgery |
| Zdroj: | Physiological Reports |
| ISSN: | 2051-817X |
| DOI: | 10.14814/phy2.14663 |
| Popis: | Hypoxia is common with preterm birth and may lead to long‐term effects on adult pancreatic endocrine function and insulin sensitivity. This phenomenon may be sexually dimorphic due to the hypoxia‐induced augmentation of the neonatal androgen surge in male newborns. We evaluated this phenomenon by pretreating neonatal rats on postnatal days (PD) 1, 6, 13, or 20 with flutamide (a nonsteroidal androgen receptor antagonist) at a standard or a high dose (10 or 50 mg/kg) compared to vehicle control. One day later, neonatal rats were exposed to either acute normoxic or hypoxic separation (fasting) for 90 min, and blood was sampled for the measurement of insulin and glucose and the calculation of HOMA‐IR as an index of insulin resistance. During normoxic and hypoxic separation (fasting), flutamide increased insulin secretion in PD2, PD7, and PD14 pups, high dose flutamide attenuated insulin secretion, and high dose flutamide attenuated the increase in HOMA‐IR due to hypoxia. Our studies suggest a unique role of the androgen receptor in the control of neonatal pancreatic function, possibly by blocking a direct effect of neonatal testosterone or in response to indirect regulatory effects of androgens on insulin sensitivity. Hypoxia is common with preterm birth and may lead to long‐term effects on adult pancreatic endocrine function and insulin sensitivity. This phenomenon may be sexually dimorphic due to the hypoxia‐induced augmentation of the neonatal androgen surge in male newborns. Our studies suggest a unique role of the androgen receptor in the control of neonatal pancreatic function, possibly by blocking a direct effect of neonatal testosterone or in response to indirect regulatory effects of androgens on insulin sensitivity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text