title: Oral salmon calcitonin attenuates hyperglycaemia and preserves pancreatic beta-cell area and function in Zucker diabetic fatty rats.
abstract: OBJECTIVE
  Oral salmon calcitonin (sCT), a dual-action amylin and calcitonin receptor agonist, improved glucose homeostasis in diet-induced obese rats. Here, we have evaluated the anti-diabetic efficacy of oral sCT using parameters of glycaemic control and beta-cell morphology in male Zucker diabetic fatty (ZDF) rats, a model of type 2 diabetes.
  
  
  METHODS
  Male ZDF rats were treated with oral sCT (0.5, 1.0 or 2 mg·kg(-1) ) or oral vehicle twice daily from age 8 to 18 weeks. Zucker lean rats served as control group. Fasting and non-fasted blood glucose, glycosylated haemoglobin (HbA1c) and levels of pancreas and incretin hormones were determined. Oral glucose tolerance test and i.p. glucose tolerance test were compared, and beta-cell area and function were evaluated.
  
  
  RESULTS
  Oral sCT treatment dose-dependently attenuated fasting and non-fasted hyperglycaemia during the intervention period. At the end of the study period, oral sCT treatment by dose decreased diabetic hyperglycaemia by ∼9 mM and reduced HbA1c levels by 1.7%. Furthermore, a pronounced reduction in glucose excursions was dose-dependently observed for oral sCT treatment during oral glucose tolerance test. In addition, oral sCT treatment sustained hyperinsulinaemia and attenuated hyperglucagonaemia and hypersecretion of total glucagon-like peptide-1 predominantly in the basal state. Lastly, oral sCT treatment dose-dependently improved pancreatic beta-cell function and beta-cell area at study end.
  
  
  CONCLUSIONS
  Oral sCT attenuated diabetic hyperglycaemia in male ZDF rats by improving postprandial glycaemic control, exerting an insulinotropic and glucagonostatic action in the basal state and by preserving pancreatic beta-cell function and beta-cell area.
authors.affiliation: Nordic Bioscience, Herlev, Denmark Diabetes Research Centre, Department of Endocrinology M, Odense University Hospital, Odense, Denmark. mjf@nordicbioscience.com
authors.forename: M
authors.initials: M
authors.lastname: Feigh
authors.forename: K V
authors.initials: KV
authors.lastname: Andreassen
authors.forename: A V
authors.initials: AV
authors.lastname: Neutzsky-Wulff
authors.forename: S T
authors.initials: ST
authors.lastname: Petersen
authors.forename: C
authors.initials: C
authors.lastname: Hansen
authors.forename: A C
authors.initials: AC
authors.lastname: Bay-Jensen
authors.forename: J E
authors.initials: JE
authors.lastname: Henriksen
authors.forename: H
authors.initials: H
authors.lastname: Beck-Nielsen
authors.forename: C
authors.initials: C
authors.lastname: Christiansen
authors.forename: K
authors.initials: K
authors.lastname: Henriksen
authors.forename: M A
authors.initials: MA
authors.lastname: Karsdal
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002116:Calcitonin / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D011924:Rats, Zucker
chemical_list: D001786:Blood Glucose; D002116:Calcitonin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; C028815:salmon calcitonin