title: Central prolactin modulates insulin sensitivity and insulin secretion in diabetic rats.
abstract: BACKGROUND
  Prolactin secretion is self-regulating as it acts upon hypothalamic dopaminergic systems which inhibit prolactin release from the anterior pituitary. Circulating prolactin improves glucose homeostasis by increasing insulin action and secretion, but central prolactin effects on glucose homeostasis have not been examined. Here, we determined that chronic central infusion of prolactin modulates insulin resistance and β-cell function and mass in 90% of pancreatectomized diabetic male rats.
  
  
  METHODS
  Diabetic rats were divided into three groups according to the dose of intracerebroventricular infusion of prolactin during 4 weeks: (1) low-dose prolactin (Low-PRL; 0.1 µg/h), (2) high-dose prolactin (High-PRL; 1 µg/h) and (3) vehicle only (cerebrospinal fluid). Nondiabetic rats were centrally infused with the vehicle.
  
  
  RESULTS
  Chronic intracerebroventricular infusion of Low-PRL lowered body weight and epididymal fat pads by increasing hypothalamic dopamine levels that reduced serum prolactin levels and potentiated leptin signaling. However, High-PRL slightly exacerbated energy dysregulation, decreased hypothalamic dopamine levels, and elevated serum prolactin levels. Both dosages promoted β-cell mass but in a different manner: Low-PRL decreased β-cell apoptosis, whereas High-PRL increased its proliferation. However, only Low-PRL enhanced first-phase insulin secretion and improved insulin sensitivity at a hyperglycemic state in comparison to the control. Low-PRL also increased glucose infusion rates and decreased hepatic glucose output in hyperinsulinemic states, signifying an improvement in hepatic insulin sensitivity. However, High-PRL exacerbated hepatic insulin resistance compared with the control diabetic rats.
  
  
  CONCLUSIONS
  In contrast to the exacerbation of insulin resistance caused by High-PRL, Low-PRL may improve energy and glucose metabolism by increasing hypothalamic dopamine levels in diabetic rats.
authors.affiliation: Department of Food and Nutrition, Obesity/Diabetes Research Center, Asan, Korea.
authors.forename: Sunmin
authors.initials: S
authors.lastname: Park
authors.forename: Suna
authors.initials: S
authors.lastname: Kang
authors.forename: Hye-Won
authors.initials: HW
authors.lastname: Lee
authors.forename: Byoung Seob
authors.initials: BS
authors.lastname: Ko
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D057967:Infusions, Intraventricular; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D008297:Male; D010180:Pancreatectomy; D011388:Prolactin / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011388:Prolactin