title: Oral salmon calcitonin protects against impaired fasting glycemia, glucose intolerance, and obesity induced by high-fat diet and ovariectomy in rats.
abstract: OBJECTIVE
  Oral salmon calcitonin (sCT) has demonstrated clinical efficacy in treating osteoporosis in postmenopausal women. The postmenopausal state is also associated with obesity-related insulin resistance (IR) and type 2 diabetes. The aim of this study was to investigate the preventive effects of oral sCT on energy and glucose homeostasis in high-fat diet (HFD)- and ovariectomy (OVX)-induced obese rats. Furthermore, the weight-regulatory and gluco-regulatory effects of short-term oral sCT intervention on HFD-induced obese rats were explored.
  
  
  METHODS
  For prevention, female rats exposed to HFD with or without OVX were treated with oral sCT for 5 weeks. As intervention, HFD-induced obese male rats were treated with oral sCT for 4 days. Body weight, food intake, and plasma glucose, insulin, and leptin levels were measured, and the clinical homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated. In addition, oral glucose tolerance was evaluated in the systemic and portal circulations.
  
  
  RESULTS
  For prevention, oral sCT reduced body weight by ∼16% to 19% (P < 0.001), reduced plasma insulin and leptin by ∼50%, and improved impaired fasting glycemia (P < 0.05) concomitantly with amelioration of IR (HOMA-IR; P < 0.01) in HFD- and OVX-induced obesity. Furthermore, oral sCT significantly reduced the incremental area under the curve for plasma glucose and insulin by ∼40% and ∼70%, respectively, during glucose tolerance testing. As intervention in HFD-induced obese rats, oral sCT reduced body weight, fasting glycemia, and insulinemia in conjunction with HOMA-IR (P < 0.001). Finally, oral sCT alleviated glucose intolerance predominantly in the portal circulation.
  
  
  CONCLUSIONS
  Oral sCT treatment displays weight-regulatory and glucoregulatory efficacy in HFD- and OVX-induced obese rats, indicating the clinical usefulness of oral sCT in postmenopausal obesity-related IR and type 2 diabetes.
authors.affiliation: Nordic Bioscience, Herlev, Denmark. mjf@nordicbioscience.com
authors.forename: Michael
authors.initials: M
authors.lastname: Feigh
authors.forename: Kim V
authors.initials: KV
authors.lastname: Andreassen
authors.forename: Sara T
authors.initials: ST
authors.lastname: Hjuler
authors.forename: Rasmus H
authors.initials: RH
authors.lastname: Nielsen
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
authors.forename: Kim
authors.initials: K
authors.lastname: Henriksen
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D001835:Body Weight; D002116:Calcitonin / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control; D059305:Diet, High-Fat; D005215:Fasting; D005260:Female; D018149:Glucose Intolerance / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; C028815:salmon calcitonin; D002116:Calcitonin