{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T03:03:09Z","timestamp":1780455789955,"version":"3.54.1"},"reference-count":57,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2014,1,1]]},"abstract":"<jats:p> Intrauterine growth-restricted (IUGR) fetuses experience prolonged hypoxemia, hypoglycemia, and elevated norepinephrine (NE) concentrations, resulting in hypoinsulinemia and \u03b2-cell dysfunction. Previously, we showed that acute adrenergic blockade revealed enhanced insulin secretion responsiveness in the IUGR fetus. To determine whether chronic exposure to NE alone enhances \u03b2-cell responsiveness afterward, we continuously infused NE into fetal sheep for 7 days and, after terminating the infusion, evaluated glucose-stimulated insulin secretion (GSIS) and glucose-potentiated arginine-induced insulin secretion (GPAIS). During treatment, NE-infused fetuses had greater ( P &lt; 0.05) plasma NE concentrations and exhibited hyperglycemia ( P &lt; 0.01) and hypoinsulinemia ( P &lt; 0.01) compared with controls. GSIS during the NE infusion was also reduced ( P &lt; 0.05) compared with pretreatment values. GSIS and GPAIS were approximately fourfold greater ( P &lt; 0.01) in NE fetuses 3 h after the 7 days that NE infusion was discontinued compared with age-matched controls or pretreatment GSIS and GPAIS values of NE fetuses. In isolated pancreatic islets from NE fetuses, mRNA concentrations of adrenergic receptor isoforms (\u03b1<jats:sub>1D<\/jats:sub>, \u03b1<jats:sub>2A<\/jats:sub>, \u03b1<jats:sub>2C<\/jats:sub>, and \u03b2<jats:sub>1<\/jats:sub>), G protein subunit-\u03b1<jats:sub>i-2<\/jats:sub>, and uncoupling protein 2 were lower ( P &lt; 0.05) compared with controls, but \u03b2-cell regulatory genes were not different. Our findings indicate that chronic exposure to elevated NE persistently suppresses insulin secretion. After removal, NE fetuses demonstrated a compensatory enhancement in insulin secretion that was associated with adrenergic desensitization and greater stimulus-secretion coupling in pancreatic islets. <\/jats:p>","DOI":"10.1152\/ajpendo.00517.2013","type":"journal-article","created":{"date-parts":[[2013,11,20]],"date-time":"2013-11-20T00:36:46Z","timestamp":1384907806000},"page":"E58-E64","source":"Crossref","is-referenced-by-count":42,"title":["Enhanced insulin secretion responsiveness and islet adrenergic desensitization after chronic norepinephrine suppression is discontinued in fetal sheep"],"prefix":"10.1152","volume":"306","author":[{"given":"Xiaochuan","family":"Chen","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Southwest University, Chongqing, China; and"},{"name":"School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice 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