title: Serum prolactin concentrations determine whether they improve or impair β-cell function and insulin sensitivity in diabetic rats.
abstract: BACKGROUND
  Prolactin improves glucose homeostasis by increasing β-cell mass under certain conditions such as pregnancy, whereas hyperprolactinaemia due to a pituitary gland adenoma tumour exacerbates insulin resistance. However, previous studies have not evaluated how prolactin modulates β-cell function and insulin sensitivity at different dosages. Here, we determined that chronic intraperitoneal injections of different dosages of prolactin have opposite effects on insulin resistance and β-cell function and mass in 90% pancreatectomized diabetic male rats, and the mechanisms were explored.
  
  
  METHODS
  Diabetic rats were divided into three groups according to the dose of intraperitoneally injected prolactin for 4 weeks: (1) low dose of prolactin (25 µg/kg bw/12 h), (2) high dose of prolactin (250 µg/kg bw/12 h), and (3) vehicle. As a non-diabetic control group, sham-operated rats were injected with vehicle.
  
  
  RESULTS
  Chronic high- and low-dose prolactin injections elevated serum prolactin levels by 2.5- and 11.8-fold, respectively. Both dosages promoted β-cell mass by increasing β-cell proliferation and neogenesis through the potentiation of phosphorylation of signal transducer and activator of transcription 5 and decreased menin expression in diabetic rats. However, only the low-dose prolactin injection potentiated glucose-stimulated insulin secretion though glucokinase and glucose transporter 2 induction in the diabetic rats. In addition, low-dose prolactin decreased hepatic glucose output in hyperinsulinaemic states, indicating an improvement in hepatic insulin resistance. However, the high-dose prolactin injection exacerbated whole-body and hepatic insulin resistance in diabetic rats.
  
  
  CONCLUSIONS
  In contrast to the normal adaptive increases in glucose-stimulated insulin secretion through expanded β-cell mass and insulin sensitivity realized with moderately increased prolactin levels, high levels of prolactin exacerbate insulin resistance and impair the insulin-secretory capacity in diabetic mice.
authors.affiliation: College of Natural Sciences, Department of Food & Nutrition, Obesity/Diabetes Research Center, Institutes of Basic Science, Hoseo University, Asan-Si, South Korea. smpark@hoseo.edu
authors.forename: Sunmin
authors.initials: S
authors.lastname: Park
authors.forename: Da Sol
authors.initials: DS
authors.lastname: Kim
authors.forename: James W
authors.initials: JW
authors.lastname: Daily
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010180:Pancreatectomy; D011388:Prolactin / Q000008:administration & dosage* / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D013739:Testosterone; D011388:Prolactin; D005934:Glucagon; D006854:Hydrocortisone